bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating the wood density of species for carbon stock assessments
Authors: Flores Olivier , Coomes David A. 
Published: October 2010

Summary1. Studies of forest carbon stocks and fluxes rely on estimates of specific wood density to convert tree diameter and height measurements made within permanent plots into carbon stock estimates. However, measurements of wood density are often available for only a subset of species. As there is strong phylogenetic trait conservatism of wood density, missing data are usually estimated by averaging the wood densities of other species within the same genus or family, using whatever data are available locally.2. The Global Wood Density (GWD) database (http://hdl.handle.net/10255/dryad.235) provides wood densities for 8412 species from around the world, providing an opportunity to utilize data from further afield when faced with missing values in a study area. We investigated whether the GWD provides better estimates than local data sets when conventional averaging methods (AM) are used. Secondly, we develop Hierarchical Bayesian Models (HBM) that incorporate phylogenetic covariance to estimate missing wood densities.3. Using AM, we found that correlations between observations and estimates were higher when the GWD was used in place of local data sets, mostly because of larger sample size. Missing wood densities were more accurately estimated from the global data set than from local data sets, indicating that the GWD should be used as a common standard when calculating carbon stocks.4. Estimates based on including phylogenetic dependency in HBMs were also closely correlated to observations, but were no better than those obtained from the simpler AM. Estimations based on HBM could become more useful when phylogenetic trees resolved to the species level are available. Until such improvements are made, we conclude that building more data into the reference data set, rather than improving the method itself, is the most productive way to refine estimates of unknown wood densities.
Overexpression of
patA
and
patB
, Which Encode ABC Transporters, Is Associated with Fluoroquinolone Resistance in Clinical Isolates of
Streptococcus pneumoniae
Authors: Garvey Mark I. , Baylay Alison J. , Wong Ryan L. , Piddock Laura J. V. 
Published: October 2010

ABSTRACT

Fifty-seven clinical isolates of
Streptococcus pneumoniae
were divided into four groups based on their susceptibilities to the fluoroquinolones ciprofloxacin and norfloxacin and the dyes ethidium bromide and acriflavine. Comparative reverse transcription-PCR was used to determine the level of expression of the genes
patA
and
patB
, which encode putative ABC transporters. Overexpression was observed in 14 of the 15 isolates that were resistant to both fluoroquinolones and dyes and in only 3 of 24 of those resistant to fluoroquinolones only. Isolates overexpressing
patA
and
patB
accumulated significantly less of the fluorescent dye Hoechst 33342 than wild-type isolates, suggesting that PatA and PatB are involved in efflux. Inactivation of
patA
and
patB
by
in vitro mariner
mutagenesis conferred hypersusceptibility to ethidium bromide and acriflavine in all isolates tested and lowered the MICs of ciprofloxacin in the
patAB
-overproducing and/or fluoroquinolone-resistant isolates. These data represent the first observation of overexpression of
patA
and
patB
in clinical isolates and show that PatA and PatB play a clinically relevant role in fluoroquinolone resistance.
Plasma and Intracellular (Peripheral Blood Mononuclear Cells) Pharmacokinetics of Once-Daily Raltegravir (800 Milligrams) in HIV-Infected Patients
Authors: Moltó José , Valle Marta , Back David , Cedeño Samandhy , Watson Victoria , Liptrott Neill , Egan Deirdre , Miranda Cristina , Barbanoj Manuel J. , Clotet Bonaventura 
Published: October 2010

ABSTRACT

The aim of this study was to evaluate the plasma and intracellular pharmacokinetics of raltegravir in HIV-infected patients receiving once-daily raltegravir. Five HIV-infected patients on stable therapy with lopinavir-ritonavir monotherapy whose HIV-1 RNA load was <50 copies/ml were included in this open-label, pilot study. Raltegravir was added to the antiretroviral regimen at a dose of 800 mg once daily from days 0 to 10. On day 10, a full pharmacokinetic profile was obtained for each participant. Raltegravir concentrations in plasma and peripheral blood mononuclear cells (PBMCs) were determined by high-performance liquid chromatography with a fluorescence detector and by liquid chromatography-tandem mass spectrometry (LC-MS/MS), respectively. The values of the raltegravir pharmacokinetic parameters in plasma and PBMCs were calculated by noncompartmental analysis. Raltegravir was well tolerated, and all participants completed the study. No differences in the times to the maximum concentration of raltegravir in plasma or the raltegravir half-lives were observed between plasma and PBMCs. The geometric mean raltegravir maximum concentration, the concentration at the end of the dosing interval, and the area under the concentration-time curve during the dose interval in plasma versus PBMCs were 2,640 ng/ml (range, 887 to 10,605 ng/ml) versus 199 ng/ml (range, 82 to 857 ng/ml) (geometric mean ratio [GMR], 13.30; 95% confidence interval [CI], 3.11 to 56.89;
P
= 0.003); 89 ng/ml (range, 51 to 200 ng/ml) versus 7 ng/ml (range, 2 to 15 ng/ml) (GMR, 13.21; 95% CI, 3.94 to 44.26;
P
= 0.001); and 12,200 ng·h/ml (range, 5,152 to 30,130 ng·h/ml) versus 909 ng·h/ml (range, 499 to 2,189 ng·h/ml) (GMR, 13.43; 95% CI, 5.13 to 35.16;
P
< 0.001), respectively. Raltegravir does not accumulate in PBMCs, with intracellular concentrations being about 1/10 of the concentrations in plasma. Despite once-daily dosing, mean raltegravir concentrations at the end of the dosing interval in plasma and PBMCs exceeded the reported protein-binding-adjusted 95% inhibitory concentration (IC
95
) and IC
50
for wild-type viral strains, respectively.
In Vivo
and
In Vitro
Efficacy of Chloroquine against
Plasmodium malariae
and
P. ovale
in Papua, Indonesia
Authors: Siswantoro H. , Russell B. , Ratcliff A. , Prasetyorini B. , Chalfein F. , Marfurt J. , Kenangalem E. , Wuwung M. , Piera K. A. , Ebsworth E. P. , Anstey N. M. , Tjitra E. , Price R. N. 
Published: October 2010

ABSTRACT

Reports of potential drug-resistant strains of
Plasmodium malariae
in western Indonesia raise concerns that chloroquine resistance may be emerging in
P. malariae
and
P. ovale
. In order to assess this,
in vivo
and
in vitro
efficacy studies were conducted in patients with monoinfection in Papua, Indonesia. Consecutive patients with uncomplicated malaria due to
P. ovale
or
P. malariae
were enrolled in a prospective clinical trial, provided with supervised chloroquine treatment, and followed for 28 days. Blood from patients with
P. malariae
or
P. ovale
parasitemia greater than 1,000 per microliter underwent
in vitro
antimalarial drug susceptibility testing using a modified schizont maturation assay. Of the 57 evaluable patients in the clinical study (
P. malariae
,
n
= 46;
P. ovale
,
n
= 11), none had recurrence with the same species during follow-up. The mean parasite reduction ratio at 48 h was 86 (95% confidence interval [CI], 57 to 114) for
P. malariae
and 150 (95% CI, 54 to 245) for
P. ovale
(
P
= 0.18). One patient infected with
P. malariae
, with 93% of parasites at the trophozoite stage, was still parasitemic on day 4.
In vitro
drug susceptibility assays were carried out successfully for 40 isolates (34 infected with
P. malariae
and 6 with
P. ovale
). The
P. malariae
infections at trophozoite stages had significantly higher chloroquine 50% effective concentrations (EC
50
s) (median, 127.9 nM [range, 7.9 to 2,980]) than those initially exposed at the ring stage (median, 14.0 nM [range, 3.5 to 27.0];
P
= 0.01). The EC
50
for chloroquine in
P. ovale
was also higher in an isolate initially at the trophozoite stage (23.2 nM) than in the three isolates predominantly at ring stage (7.8 nM). Chloroquine retains adequate efficacy against
P. ovale
and
P. malariae
, but its marked stage specificity of action may account for reports of delayed parasite clearance times.
A Novel Insertion Sequence, IS
Aba10
, Inserted into IS
Aba1
Adjacent to the
bla
OXA-23
Gene and Disrupting the Outer Membrane Protein Gene
carO
in
Acinetobacter baumannii
Authors: Lee Yangsoon , Kim Chang-Ki , Lee Hyukmin , Jeong Seok Hoon , Yong Dongeun , Lee Kyungwon 
Published: October 2010

ABSTRACT

We investigated an outbreak caused by carbapenem-resistant
Acinetobacter baumannii
carrying the
bla
OXA-23
gene. A novel insertion sequence (IS), named IS
Aba10
, was found to be inserted into the IS
Aba1
element preceding the
bla
OXA-23
gene in a group of isolates showing higher carbapenem MICs. The presence of IS
Aba10
was associated with increased OXA-23 expression, likely by providing additional promoter sequences. IS
Aba10
was also inserted into the
carO
outer membrane protein gene in most of these isolates.
Leukocytes Infiltrate the Skin and Draining Lymph Nodes in Response to the ProtozoanLeishmania infantum chagasi
Authors: Thalhofer Colin J. , Chen Yani , Sudan Bayan , Love-Homan Laurie , Wilson Mary E. 
Published: October 2010

ABSTRACTThe vector-borne protozoanLeishmania infantum chagasicauses minimal inflammation after inoculation into skin but disseminates to cause fatal visceral leishmaniasis. To define the inflammatory response at the parasite inoculation site, we introduced metacyclicL. infantum chagasipromastigotes intradermally into BALB/c mouse ears and studied inflammatory cells over 7 days. Ly6G+neutrophils rapidly infiltrated the dermis, peaking after 6 to 24 h. Macrophages and NK cells next infiltrated the dermis, and NK followed by B cells expanded in draining lymph nodes. Parasite-containing phagocytes were tracked with fluorescent mCherry-labeledL. infantum chagasi.Ly6G+neutrophils contained the greatest proportion of intracellular parasites 6 to 24 h after inoculation, whereas dermal macrophages harbored the majority of intracellular parasites after 2 to 7 days. These observations were validated microscopically. Low doses of antibody transiently depleted mice of neutrophils, leaving other cells intact. Combined results ofin vivoimaging, flow cytometry, and quantitative PCR showed that neutrophil depletion slowed the clearance of extracellular (luciferase-positive) promastigotes during the first 24 h after inoculation yet decreased the numbers of leukocytes containing intracellular (mCherry-positive) parasites. From 3 days onward, totalL. infantum chagasi-containing dermal leukocytes and totalL. infantum chagasiparasites in draining lymph nodes were similar in both groups. Nonetheless, a second wave ofL. infantum chagasi-containing neutrophils occurred 7 days after parasite inoculation into neutrophil-depleted mice, corresponding to the time of neutrophil recovery. Thus, neutrophils were recruited to the dermis even late after inoculation, andL. infantum chagasitrafficked through neutrophils in both neutrophil-depleted and control mice, albeit with different kinetics. Recruitment of neutrophils and transient parasite residence in neutrophils may play a role in nonulcerative forms of leishmaniasis.
Surgeons' opinions and practice of informed consent in Nigeria
Authors: Ogundiran Temidayo O , Adebamowo Clement A 
Published: October 2010

BackgroundInformed consent is perhaps more relevant to surgical specialties than to other clinical disciplines. Fundamental to this concept is the provision of relevant information for the patient to make an informed choice about a surgical intervention. The opinions of surgeons in Nigeria about informed consent in their practice were surveyed.MethodsA cross-sectional survey of surgeons in Nigeria was undertaken in 2004/5 using self-administered semistructured questionnaires.ResultsThere were 102 respondents, 85.3% of whom were men and 58.8% were aged 31–40 years. 43.1% were consultants and 54.0% were surgical trainees. 27.4% were in surgical subspecialties, 26.5% in general surgery and 21.6% were obstetricians and gynaecologists. 54.9% agreed that sufficient information is not provided to patients while obtaining their consent for surgical procedures. They listed medicolegal reasons (70.6%), informing patients about benefits, risks and alternatives (64.7%) and hospital policy (50.0%) as some reasons for obtaining consent for surgical procedures. When patients decline to give consent for surgery, 84.3% of them thought that poor communication between surgeons and patients may be contributory. They identified taking a course in bioethics during surgical training and compulsory communication skills course as some ways to improve communication between surgeons and patients.ConclusionMost Nigerian surgeons seemed to have a good knowledge of the informed consent requirements and process but fall short in practice. There is a need to improve the surgeon–patient relationship in line with modern exigencies to provide interactive environments for fruitful patient communication and involvement.
Enhanced Genetic Instability and Dasatinib Sensitivity in Mammary Tumor Cells Lacking NEDD9
Authors: Singh Mahendra K. , Izumchenko Eugene , Klein-Szanto Andres J. , Egleston Brian L. , Wolfson Marina , Golemis Erica A. 
Published: October 2010

Abstract
Elevated expression of the NEDD9/HEF1/Cas-L scaffolding protein promotes tumor cell invasion and metastasis in multiple cancer cell types. Conversely, generation of mammary tumors in the mouse mammary tumor virus (MMTV)-polyoma virus middle T (PyVT) genetic model is delayed by a Nedd9−/− genotype. These activities arise from the role of NEDD9 in assembling complexes and supporting activity of cancer signaling proteins, including FAK, Src, Shc, and AKT, and would support evaluation of NEDD9 expression as an unambiguous biomarker for tumor aggressiveness. However, we here show that despite the initial delay in tumor growth, cells derived from MMTV-PyVT;Nedd9−/− tumors are characteristically hyperaggressive versus MMTV-PyVT;Nedd9+/+ cells in anchorage-independent growth, in growth on three-dimensional matrix produced by tumor-associated fibroblasts, and in formation of tumors after mammary orthotopic reinjection and of lung metastases after tail vein injection. This reversal suggests the specific selection of MMTV-PyVT;Nedd9−/− cells for growth in an in vivo microenvironment. Indeed, MMTV-PyVT;Nedd9−/− cells have increased cell cycle, centrosomal, and mitotic defects, phenotypes compatible with the increased selection of these cells for aggressive growth. Intriguingly, in spite of their aggressive phenotype, MMTV-PyVT;Nedd9−/− cells persistently have low levels of Src activation and are hypersensitive to the Src kinase inhibitor dasatinib. These studies identify NEDD9 as a complex modulator of different aspects of mammary tumor growth. Cancer Res; 70(21); 8907–16. ©2010 AACR.
BRCA1-IRIS Overexpression Promotes Cisplatin Resistance in Ovarian Cancer Cells
Authors: Chock Kerri L. , Allison Jamie M.S. , Shimizu Yoshiko , ElShamy Wael M. 
Published: October 2010

Abstract
Evasion of apoptosis plays a key role in cancer development, drug resistance, and recurrence. The BRCA1 locus product protein BRCA1-IRIS is overexpressed in several cisplatin-resistant ovarian cancer cell lines, but its relationship to resistance is uncertain. Here, we show that in human ovarian surface epithelial (HOSE) cells, overexpression of BRCA1-IRIS triggers expression of the antiapoptotic protein survivin. Negative modulation of phosphatidylinositol 3-kinase (PI3K) signaling or AKT silencing reduced survivin expression in this setting. Conversely, silencing BRCA1-IRIS in ovarian cancer cell lines derepressed PTEN expression along with the antiapoptotic AKT targets FOXO1 and FOXO3a, suppressing survivin expression. Cisplatin (≤50 μmol/L) exposure was sufficient to activate expression of the BRCA1-IRIS-AKT-survivin cascade in HOSE cells, whereas under similar conditions cisplatin failed to induce apoptosis in ovarian cancer cell lines expressing this regulatory cascade. Mechanistic investigations indicated that BRCA1-IRIS triggers survivin expression through a PI3K/AKT-dependent pathway involving NF-κB, but also through a PI3K/AKT-independent pathway involving PTEN, FOXO1, and FOXO3a. Our findings indicate how BRCA1-IRIS overexpression prevents chemotherapy-induced cell death by upregulating expression of survivin, and they highlight this regulatory cascade as a candidate focus to improve treatment of advanced drug-resistant ovarian cancers. Cancer Res; 70(21); 8782–91. ©2010 AACR.
Prostate Cancer Radiosensitization through Poly(ADP-Ribose) Polymerase-1 Hyperactivation
Authors: Dong Ying , Bey Erik A. , Li Long-Shan , Kabbani Wareef , Yan Jingsheng , Xie Xian-Jin , Hsieh Jer-Tsong , Gao Jinming , Boothman David A. 
Published: October 2010

Abstract
The clinical experimental agent, β-lapachone (β-lap; Arq 501), can act as a potent radiosensitizer in vitro through an unknown mechanism. In this study, we analyzed the mechanism to determine whether β-lap may warrant clinical evaluation as a radiosensitizer. β-Lap killed prostate cancer cells by NAD(P)H:quinone oxidoreductase 1 (NQO1) metabolic bioactivation, triggering a massive induction of reactive oxygen species, irreversible DNA single-strand breaks (SSB), poly(ADP-ribose) polymerase-1 (PARP-1) hyperactivation, NAD+/ATP depletion, and μ-calpain–induced programmed necrosis. In combination with ionizing radiation (IR), β-lap radiosensitized NQO1+ prostate cancer cells under conditions where nontoxic doses of either agent alone achieved threshold levels of SSBs required for hyperactivation of PARP-1. Combination therapy significantly elevated SSB level, γ-H2AX foci formation, and poly(ADP-ribosylation) of PARP-1, which were associated with ATP loss and induction of μ-calpain–induced programmed cell death. Radiosensitization by β-lap was blocked by the NQO1 inhibitor dicoumarol or the PARP-1 inhibitor DPQ. In a mouse xenograft model of prostate cancer, β-lap synergized with IR to promote antitumor efficacy. NQO1 levels were elevated in ∼60% of human prostate tumors evaluated relative to adjacent normal tissue, where β-lap might be efficacious alone or in combination with radiation. Our findings offer a rationale for the clinical utilization of β-lap (Arq 501) as a radiosensitizer in prostate cancers that overexpress NQO1, offering a potentially synergistic targeting strategy to exploit PARP-1 hyperactivation. Cancer Res; 70(20); 8088–96. ©2010 AACR.
Cell Signaling by Urokinase-type Plasminogen Activator Receptor Induces Stem Cell–like Properties in Breast Cancer Cells
Authors: Jo Minji , Eastman Boryana M. , Webb Drue L. , Stoletov Konstantin , Klemke Richard , Gonias Steven L. 
Published: October 2010

Abstract
Signaling by urokinase-type plasminogen activator receptor (uPAR) can cause epithelial-mesenchymal transition (EMT) in cultured breast cancer cells. In this report, we show that uPAR signaling can also induce cancer stem cell (CSC)–like properties. Ectopic overexpression of uPAR in human MDA-MB-468 breast cancer cells promoted the emergence of a CD24−/CD44+ phenotype, characteristic of CSCs, while increasing the cell surface abundance of integrin subunits β1/CD29 and α6/CD49f that represent putative mammary gland stem cell biomarkers. uPAR overexpression increased mammosphere formation in vitro and tumor formation in an immunocompromized severe combined immunodeficient (SCID) mouse model of orthotopic breast cancer. Hypoxic conditions that are known to induce EMT in MDA-MB-468 cells also increased cell surface β1/CD29, mimicking the effects of uPAR overexpression. Antagonizing uPAR effector signaling pathways reversed the increase in cell surface integrin expression. Whereas uPAR overexpression did not induce EMT in MCF-7 breast cancer cells, CSC-like properties were nevertheless still induced along with an increase in tumor initiation and growth in the orthotopic setting in SCID mice. Notably, in MCF-7 cell mammospheres, which display a well-defined acinus-like structure with polarized expression of E-cadherin and β1-integrin, cell collapse into the central cavity was decreased by uPAR overexpression, suggesting that uPAR signaling may stabilize epithelial morphology. In summary, our findings show that uPAR signaling can induce CSC-like properties in breast cancer cells, either concomitantly with or separately from EMT. Cancer Res; 70(21); 8948–58. ©2010 AACR.
TRAIL-Induced Apoptosis Is Preferentially Mediated via TRAIL Receptor 1 in Pancreatic Carcinoma Cells and Profoundly Enhanced by XIAP Inhibitors
Authors: Stadel Dominic , Mohr Andrea , Ref Caroline , MacFarlane Marion , Zhou Shaoxia , Humphreys Robin , Bachem Max , Cohen Gerry , Möller Peter , Zwacka Ralf M. , Debatin Klaus-Michael , Fulda Simone 
Published: October 2010

Abstract
Purpose: We previously reported that small molecule X-linked inhibitor of apoptosis (XIAP) inhibitors synergize with soluble TRAIL to trigger apoptosis in pancreatic carcinoma cells. Because cancers may preferentially signal via 1 of the 2 agonistic TRAIL receptors, we investigated these receptors as a therapeutic target in pancreatic cancer in the present study.
Experimental Design: We examined TRAIL receptor expression and cytotoxicity of specific monoclonal antibodies to TRAIL-R1 (HGS-ETR1, mapatumumab) or TRAIL-R2 (HGS-ETR2, lexatumumab) and of TRAIL receptor selective mutants alone and in combination with small molecule XIAP inhibitors in pancreatic cancer cell lines, in primary specimens, and in a xenotransplant model in vivo.
Results: The majority of primary pancreatic carcinoma samples and all cell lines express one or both agonistic TRAIL receptors. Nine of 13 cell lines are more sensitive to mapatumumab-induced apoptosis, whereas lexatumumab requires cross-linking for maximal activity. Similarly, TRAIL-R1 selective mutants display higher cytotoxicity than TRAIL-R2 selective mutants. Small molecule XIAP inhibitors preferentially act in concert with mapatumumab to trigger caspase activation, caspase-dependent apoptosis, and suppress clonogenic survival. Also, primary cultured pancreatic carcinoma cells are more susceptible to mapatumumab than lexatumumab, which is significantly enhanced by a XIAP inhibitor. Importantly, combined treatment with mapatumumab and a XIAP inhibitor cooperates to suppress tumor growth in vivo.
Conclusions: Mapatumumab exerts antitumor activity, especially in combination with XIAP inhibitors against most pancreatic carcinoma cell lines, whereas lexatumumab requires cross-linking for optimal cytotoxicity. These findings have important implications for the design of TRAIL-based protocols for pancreatic cancer. Clin Cancer Res; 16(23); 5734–49. ©2010 AACR.