bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Ecological Role and Geography of Reindeer (Rangifer tarandus) in Northern Eurasia
Authors: Forbes Bruce C. , Kumpula Timo 
Published: June 2009

AbstractThe reindeer is a ruminant of the family Cervidae with a circumpolar distribution that has been a key component of Eurasian high latitude ecosystems for at least 2 million years. Interactions with humans date from the late Pleistocene onward and wild and semi‐domestic animals continue to be highly valued by aboriginal and non‐native peoples for a diversity of purposes. As a widespread and dominant ungulate across many tundra and taiga regions, the reindeer exerts a number of important controls on ecosystem structure and function. Animals, both free‐ranging and herded, move seasonally between summer, winter and transitional spring/autumn habitats or ‘pastures’. Their effects on vegetation and soils vary greatly in space and time depending on factors such as altitude/exposure, snow depth, substrate, moisture, prevailing vegetation type and, most importantly, animal density. At present, the number of Old World reindeer is somewhat less than 2.5 million. The most productive semi‐domestic herds occur in Fennoscandia and the Nenets regions of northwest Russia straddling the Ural Mountains. Management systems differ within and among countries and regions. Given the diverse suite of factors involved, changes in vegetation associated with grazing and trampling can be remarkably heterogeneous spatially yet remain to a large extent predictable. Potential threats facing reindeer populations of Eurasia include rapid land use change, climate change and ongoing institutional conflicts.
BAALC and ERG expression in acute myeloid leukemia with normal karyotype: impact on prognosis
Authors: EID M. A. , ATTIA M. , ABDOU S. , EL‐SHAZLY S. F. , ELAHWAL L. , FARRAG W. , MAHMOUD L. 
Published: June 2009

SummaryCytogenetic aberrations are important prognostic factors in acute myeloid leukemia (AML). About 45% of de novo AML lack cytogenetic abnormalities, so identification of predictive molecular markers might improve therapy. We studied the prognostic impact of brain and acute leukemia, cytoplasmic (BAALC) and ETS‐related gene (ERG) expression in AML with normal karyotype. Pretreatment bone marrow samples from 30 cytogenetically normal AML patients were analysed for BAALC and ERG expression using real time RT‐PCR. The patients were dichotomized at BAALC and ERG mean expression into low and high expression. BAALC showed high expression in 70% of patients and its expression did not correlate with the clinical parameters of patients. ERG was high in 33.3% of patients and its expression was associated with lower ages and higher white cell counts. With follow‐up for 2 years, patients with high BAALC and high ERG had low rates of clinical remission (P < 0.005) and inferior overall survival (OS) (P < 0.001 and <0.002 for BAALC and ERG respectively). No significant association was observed between the increase in BAALC and ERG expression (P = 0.398). Multivariable analysis confirmed high BAALC expression as an independent risk factor for OS. Overexpression of BAALC and ERG either separate or concomitant predict adverse clinical outcome and may define important risk factor in cytogenetically normal AML.
One‐Sided Coverage Intervals for a Proportion Estimated from a Stratified Simple Random Sample
Authors: Kott Phillip S. , Liu Yan K. 
Published: June 2009

Summary Using an Edgeworth expansion to speed up the asymptotics, we develop one‐sided coverage intervals for a proportion based on a stratified simple random sample. To this end, we assume the values of the population units are generated from independent random variables with a common mean within each stratum. These stratum means, in turn, may either be free to vary or are assumed to be equal. The more general assumption is equivalent to a model‐free randomization‐based framework when finite population correction is ignored. Unlike when an Edgeworth expansion is used to construct one‐sided intervals under simple random sampling, it is necessary to estimate the variance of the estimator for the population proportion when the stratum means are allowed to differ. As a result, there may be accuracy gains from replacing the normal z‐score in the Edgeworth expansion with a t‐score.
Assessing oil resources in the Middle East and North Africa
Authors: Aguilera Roberto F. 
Published: June 2009

AbstractSome energy experts are concerned that the world will soon face a global crisis to dwindling oil resources and a peak in production. This paper analyses the concern by estimating a cumulative supply curve for conventional oil in the Middle East and North Africa (MENA) region. It does so by attaching production costs to the endowment volumes of oil in the region, including volumes from provinces not previously assessed. A Variable Shape Distribution model is used to estimate the volumes of the previously unassessed provinces.The findings show that MENA oil should last far longer than some concerned experts claim. In addition, the production costs are lower than current market oil prices and significantly lower than prices observed in mid‐2008.
α‐MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV‐induced DNA damage in human melanocytes
Authors: Abdel‐Malek Zalfa A. , Ruwe Andrew , Kavanagh‐Starner Renny , Kadekaro Ana Luisa , Swope Viki , Haskell‐Luevano Carrie , Koikov Leonid , Knittel James J. 
Published: June 2009

SummaryOne skin cancer prevention strategy that we are developing is based on synthesizing and testing melanocortin analogs that reduce and repair DNA damage resulting from exposure to solar ultraviolet (UV) radiation, in addition to stimulating pigmentation. Previously, we reported the effects of tetrapeptide analogs of α‐melanocortin (α‐MSH) that were more potent and stable than the physiological α‐MSH, and mimicked its photoprotective effects against UV‐induced DNA damage in human melanocytes. Here, we report on a panel of tripeptide analogs consisting of a modified α‐MSH core His6‐d‐Phe7‐Arg8, which contained different N‐capping groups, C‐terminal modifications, or arginine mimics. The most potent tripeptides in activating cAMP formation and tyrosinase of human melanocytes were three analogs with C‐terminal modifications. The most effective C‐terminal tripeptide mimicked α‐MSH in reducing hydrogen peroxide generation and enhancing nucleotide excision repair following UV irradiation. The effects of these three analogs required functional MC1R, as they were absent in human melanocytes that expressed non‐functional receptor. These results demonstrate activation of the MC1R by tripeptide melanocortin analogs. Designing small analogs for topical delivery should prove practical and efficacious for skin cancer prevention.
Fluorescence-Based Assay for Phenotypic Characterization of Human Cytomegalovirus Polymerase Mutations Regarding Drug Susceptibility and Viral Replicative Fitness
Authors: Chevillotte Meike , Schubert Axel , Mertens Thomas , von Einem Jens 
Published: June 2009

ABSTRACT
One essential prerequisite for genotypic drug susceptibility testing of human cytomegalovirus (HCMV) is the phenotypic characterization of mutations identified in the viral protein kinase gene UL97 and the viral DNA polymerase gene UL54 regarding their quantitative impact on drug susceptibility. We developed a new method for phenotypic characterization of UL54 mutations with regard to polymerase activity, viral replication, and drug susceptibility. To determine the most suitable viral indicator gene, enhanced green fluorescence protein was C-terminally fused to the HCMV early-late protein UL83 (pp65) or the late proteins UL32 (pp150) and UL99 (pp28), resulting in reporter viruses vTB65g, vTB150g, and vTB28g. vTB65g proved to be superior to the other constructs due to its favorable signal-to-noise ratio and was therefore used to establish the optimum conditions for our assay. The UL54 E756K and D413E mutations were introduced into vTB65g by markerless bacterial artificial chromosome mutagenesis, resulting in virus strains vE756Kg and vD413Eg. The drug susceptibility phenotypes of vE756Kg and vD413Eg were comparable to those previously reported. Furthermore, we found a reduced replicative fitness of vE756Kg by measuring fluorescence intensity as well as by conventional virus growth kinetics. Decreased fluorescence signals of vE756Kg- and vD413Eg-infected cells at late times of infection suggested a reduced polymerase activity, which was confirmed by real-time PCR quantification of the newly synthesized viral DNAs. This new fluorescence-based assay is a highly reproducible method for the phenotypic characterization of mutations potentially influencing drug susceptibility, viral replicative fitness, and polymerase activity of HCMV after marker transfer.
Prevalence and Characterization of Heterogeneous Vancomycin-Intermediate
Staphylococcus aureus
Isolates from 14 Cities in China
Authors: Sun Wenjia , Chen Hongbin , Liu Yudong , Zhao Chunjiang , Nichols Wright W. , Chen Minjun , Zhang Jianzhong , Ma Yue , Wang Hui 
Published: June 2009

ABSTRACT

The prevalence of heterogeneous vancomycin-intermediate
Staphylococcus aureus
(hVISA) among 1,012 vancomycin-susceptible methicillin (meticillin)-resistant
S. aureus
isolates collected from 14 cities in China from 2005 to 2007 was 13 to 16%, as determined by a combination of (i) measurement by the modified population analysis profile-area under the curve method (PAP-AUC) and (ii) estimation from the measured sensitivity and specificity of a screening method. Two hundred isolates from blood were chosen as a subset for measurement of the sensitivities and the specificities of several previously described screening methods by using the results of PAP-AUC as the reference. During this testing, one isolate was found to be a vancomycin-intermediate
S. aureus
(VISA) strain so was not used in the evaluation of the screening tests. Of the other 199 isolates, 26 (13.1%) were hVISA, as assessed by PAP-AUC. A screening cascade of culturing the isolates on brain heart infusion agar containing teicoplanin (5 mg/liter) and then subjecting the positive isolates to a macro-Etest method was applied to the 812 non-blood isolates, yielding 149 positive results. From these results and by adjusting for sensitivity (0.423) and specificity (0.861), the prevalence was estimated to be 15.7%. The precision of that estimate was assessed by reapplying the screening cascade to 120 randomly selected isolates from the 812 non-blood isolates and simultaneously determining their heterogeneous vancomycin-intermediate susceptibility status by PAP-AUC. Because PAP-AUC is impractical for use with large numbers of isolates, the screening-based estimation method is useful as a first approximation of the prevalence of hVISA. Of the 27 VISA or hVISA isolates from blood, 22.2% and 74.1% were staphylococcal chromosome cassette
mec
types II and III, respectively, while 77.8% and 22.2% were
agr
type 1 and
agr
type 2, respectively; the MIC ranges were 0.5 to 4 mg/liter for vancomycin and 0.25 to 1 mg/liter for daptomycin.
Mosaic Penicillin-Binding Protein 2 in
Neisseria gonorrhoeae
Isolates Collected in 2008 in San Francisco, California
Authors: Pandori Mark , Barry Pennan M. , Wu Abel , Ren Alyssa , Whittington William L. H. , Liska Sally , Klausner Jeffrey D. 
Published: June 2009

ABSTRACT

Using a real-time PCR assay specific for a mosaic
penA
allele that has been associated with oral cephalosporin resistance in Asia, 54 available
Neisseria gonorrhoeae
isolates collected in San Francisco, CA, from January to October 2008 were analyzed. Five isolates tested positive for the mosaic
penA
gene by real-time PCR. DNA sequencing revealed two mosaic
penA
alleles (SF-A and SF-B). Isolates with SF-A and SF-B alleles possessed elevated MICs for the oral cephalosporins cefpodoxime and cefixime.
In Vitro Susceptibilities of
Leishmania donovani
Promastigote and Amastigote Stages to Antileishmanial Reference Drugs: Practical Relevance of Stage-Specific Differences
Authors: Vermeersch Marieke , da Luz Raquel Inocêncio , Toté Kim , Timmermans Jean-Pierre , Cos Paul , Maes Louis 
Published: June 2009

ABSTRACT

The in vitro susceptibilities of the reference strain
Leishmania donovani
MHOM/ET/67/L82 to sodium stibogluconate, amphotericin B, miltefosine, and the experimental compound PX-6518 were determined for extracellular log-phase promastigotes, established axenic amastigotes, fresh spleen-derived amastigotes, and intracellular amastigotes in primary mouse peritoneal macrophages. Susceptibility to amphotericin B did not differ across the various axenic models (50% inhibitory concentrations [IC
50
], 0.6 to 0.7 μM), and amphotericin B showed slightly higher potency against intracellular amastigotes (IC
50
, 0.1 to 0.4 μM). A similar trend was observed for miltefosine, with comparable efficacies against the extracellular (IC
50
, 0.4 to 3.8 μM) and intracellular (IC
50
, 0.9 to 4.3 μM) stages. Sodium stibogluconate, used either as Pentostam or as a crystalline substance, was inactive against all axenic stages (IC
50
, >64 μg Sb
V
/ml) but showed good efficacy against intracellular amastigotes (IC
50
, 22 to 28 μg Sb
V
/ml); the crystalline substance was about two to three times more potent (IC
50
, 9 to 11 μg Sb
V
/ml). The activity profile of PX-6518 was comparable to that of sodium stibogluconate, but at a much higher potency (IC
50
, 0.1 μg/ml). In conclusion, the differential susceptibility determines which in vitro models are appropriate for either drug screening or resistance monitoring of clinical field isolates. Despite the more complex and labor-intensive protocol, the current results support the intracellular amastigote model as the gold standard for in vitro
Leishmania
drug discovery research and for evaluation of the resistance of field strains, since it also includes host cell-mediated effects. Axenic systems can be recommended only for compounds for which no cellular mechanisms are involved, for example, amphotericin B and miltefosine.
A Novel Tryptophanyl-tRNA Synthetase Gene Confers High-Level Resistance to Indolmycin
Authors: Vecchione James J. , Sello Jason K. 
Published: June 2009

ABSTRACT
Indolmycin, a potential antibacterial drug, competitively inhibits bacterial tryptophanyl-tRNA synthetases. An effort to identify indolmycin resistance genes led to the discovery of a gene encoding an indolmycin-resistant isoform of tryptophanyl-tRNA synthetase. Overexpression of this gene in an indolmycin-sensitive strain increased the indolmycin MIC 60-fold. Its transcription and distribution in various bacterial genera were assessed. The level of resistance conferred by this gene was compared to that of a known indolmycin resistance gene and to those of genes with resistance-conferring point mutations.
Pharmacokinetics and Buccal Mucosal Concentrations of a 15 Milligram per Kilogram of Body Weight Total Dose of Liposomal Amphotericin B Administered as a Single Dose (15 mg/kg), Weekly Dose (7.5 mg/kg), or Daily Dose (1 mg/kg) in Peripheral Stem Cell Transplant Patients
Authors: Gubbins Paul O. , Amsden Jarrett R. , McConnell Scott A. , Anaissie Elias J. 
Published: June 2009

ABSTRACT

The pharmacokinetics and safety of extended-interval dosing of prophylactic liposomal amphotericin B (L-AMB) in peripheral stem cell transplant recipients were evaluated. The patients received L-AMB daily at 1 mg/kg of body weight or weekly at 7.5 mg/kg or received L-AMB as a single dose (15 mg/kg). The buccal mucosal tissue concentrations of L-AMB were measured. Of the 24 patients enrolled, 5 withdrew after the initial dose due to an infusion-related reaction (
n
= 2) or significant increases in the serum creatinine (Scr) levels (
n
= 3). Weekly L-AMB dosing (7.5 mg/kg) produced mean plasma concentrations of >0.300 μg/ml for the first 7 days and >0.220 μg/ml for 7 days after the second dose. A single L-AMB dose (15 mg/kg) produced mean plasma concentrations of >0.491 μg/ml for at least 7 seven days. These concentrations are within the range of the MICs reported in the literature for susceptible strains of
Candida
and are at the lower limits of the MICs for
Aspergillus
spp. Extended-interval dosing produced buccal mucosal tissue concentrations well in excess of the MICs reported in the literature for susceptible strains of
Candida
and
Aspergillus
spp. Infusion-related reactions occurred in 24% of the patients. Baseline and end-of-study Scr, electrolyte (K
+
, Mg
2+
, PO
4
), and serum transaminase levels were similar across the dosage groups. Five (31%) patients met the nephrotoxicity definition prior to completion of the study. Patients in the weekly or single-dose groups experienced nephrotoxicity significantly faster than the patients in the daily dosing cohort. A weekly L-AMB dose (7.5 mg/kg) or a single L-AMB dose (15 mg/kg) produced sufficient concentrations in plasma and highly vascular tissue to warrant further studies of the safety, efficacy, and practicality of the weekly prophylactic administration of L-AMB.
Influence of Recombination on Development of Mutational Resistance to Linezolid in
Enterococcus faecalis
JH2-2
Authors: Boumghar-Bourtchaï Leyla , Dhalluin Anne , Malbruny Brigitte , Galopin Sébastien , Leclercq Roland 
Published: June 2009

ABSTRACT

We compared the propensities of
Enterococcus faecalis
JH2-2 and of the recombination-deficient JH2-2
recA
strain to develop mutational resistance to linezolid. In both organisms, a mutation in a single
rrl
copy conferred resistance to linezolid. Delay in acquisition of the mutation by other
rrl
copies in JH2-2
recA
showed that gene conversion contributed to the acquisition of resistance.
Functional and Immunological Characterization of a Duffy Binding-Like Alpha Domain from
Plasmodium falciparum
Erythrocyte Membrane Protein 1 That Mediates Rosetting
Authors: Mayor Alfredo , Rovira-Vallbona Eduard , Srivastava Anand , Sharma Surya K. , Pati Sudhanshu S. , Puyol Laura , Quinto Llorenç , Bassat Quique , Machevo Sonia , Mandomando Inacio , Chauhan Virander S. , Alonso Pedro L. , Chitnis Chetan E. 
Published: June 2009

ABSTRACT

The Duffy binding-like (DBL) domains are common adhesion modules present in
Plasmodium falciparum
erythrocyte membrane protein 1 (PfEMP1) variants, which are responsible for immune evasion and cytoadherence. Knowledge about how immune responses are acquired against polymorphic DBL domains of PfEMP1 can aid in the development of vaccines for malaria. A recombinant DBLα domain, encoded by R29
var1
, which binds complement receptor 1 to mediate rosetting by the
P. falciparum
laboratory strain R29, was expressed in
Escherichia coli
, renatured by oxidative refolding to its native form, and purified to homogeneity. Antibody levels in 704 plasmas obtained from residents of areas of different levels of malaria endemicity in Orissa (India) and Manhiça (Mozambique) were assessed by enzyme-linked immunosorbent assay. The refolded DBLα domain was pure, homogeneous, and functional in that it bound human erythrocytes with specificity and was capable of inhibiting rosetting. The proportion of individuals who had measurable anti-DBLα immunoglobulin G responses was low in areas of low malaria endemicity in Orissa (6.7%) but high in areas of high endemicity in Orissa (87.5%) and Manhiça (74.5%). Seroprevalence and antibody levels against the recombinant protein increased with the age of inhabitants from areas with high transmission rates (
P
< 0.001). Half of the children in these areas had seroconverted by the age of 5 years. These findings suggest that in spite of the extreme polymorphism of PfEMP1 DBLα domains, the acquisition of specific antibodies is rapid and age related and reflects the reduced risk of malaria in areas with high transmission rates. Further studies are required to elucidate the role of these antibodies in protection from malaria.
Real-Time Observation ofListeria monocytogenes-Phagocyte Interactions in Living Zebrafish Larvae
Authors: Levraud Jean-Pierre , Disson Olivier , Kissa Karima , Bonne Isabelle , Cossart Pascale , Herbomel Philippe , Lecuit Marc 
Published: June 2009

ABSTRACTThe zebrafish,Danio rerio, has become a popular vertebrate model for the study of infections, mainly because of its excellent optical accessibility at the embryonic and larval stages, when the innate immune system is already effective. We have thus tested the susceptibility of zebrafish larvae to the human pathogenListeria monocytogenes, a gram-positive, facultative, intracellular bacterium that is known to survive and multiply in professional phagocytes and that causes fatal meningitis and abortions. Intravenous injection of early zebrafish larvae resulted in a progressive and ultimately fatal infection. Blood-borneL. monocytogenesbacteria were quickly trapped and engulfed by macrophages, an event that, for the first time, could be captured in vivo and in real time. Granulocytes also participated in the innate immune response. As in mammals, bacteria could escape the macrophage phagosome in a listeriolysin-dependent manner and accessed the cytosol; this event was critical for bacterial virulence, as listeriolysin-deficient bacteria were completely avirulent. Actin comet tails and protrusions were observed, suggesting cell-to-cell spread; these phenomena also played a role in virulence in zebrafish larvae, asactA-deficient bacteria were attenuated. These results demonstrate the relevance of the genetically tractable and optically accessible zebrafish model for the study ofL. monocytogenespathogenesis and particularly for the dissection of its interactions with phagocytes in vivo, a key factor ofL. monocytogenesvirulence.
Neisseria gonorrhoeae
Infection Protects Human Endocervical Epithelial Cells from Apoptosis via Expression of Host Antiapoptotic Proteins
Authors: Follows S. A. , Murlidharan J. , Massari P. , Wetzler L. M. , Genco C. A. 
Published: June 2009

ABSTRACT

Several microbial pathogens can modulate the host apoptotic response to infection, which may contribute to immune evasion. Various studies have reported that infection with the sexually transmitted disease pathogen
Neisseria gonorrhoeae
can either inhibit or induce apoptosis.
N. gonorrhoeae
infection initiates at the mucosal epithelium, and in women, cells from the ectocervix and endocervix are among the first host cells encountered by this pathogen. In this study, we defined the antiapoptotic effect of
N. gonorrhoeae
infection in human endocervical epithelial cells (End/E6E7 cells). We first established that
N. gonorrhoeae
strain FA1090B failed to induce cell death in End/E6E7 cells. Subsequently, we demonstrated that stimulation with
N. gonorrhoeae
protected these cells from staurosporine (STS)-induced apoptosis. Importantly, only End/E6E7 cells incubated with live bacteria and in direct association with
N. gonorrhoeae
were protected from STS-induced apoptosis, while heat-killed and antibiotic-killed bacteria failed to induce protection. Stimulation of End/E6E7 cells with live
N. gonorrhoeae
induced NF-κB activation and resulted in increased gene expression of the NF-κB-regulated antiapoptotic genes
bfl-1
,
cIAP-2
, and
c-FLIP
. Furthermore, cIAP-2 protein levels also increased in End/E6E7 cells incubated with gonococci. Collectively, our results indicate that the antiapoptotic effect of
N. gonorrhoeae
in human endocervical epithelial cells results from live infection via expression of host antiapoptotic proteins. Securing an intracellular niche through the inhibition of apoptosis may be an important mechanism utilized by
N. gonorrhoeae
for microbial survival and immune evasion in cervical epithelial cells.