bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Analysis of Prevalence, Risk Factors, and Molecular Epidemiology of Antibiotic-Associated Diarrhea Due to
Clostridium difficile
,
Clostridium perfringens
, and
Staphylococcus aureus
Authors: Asha N. J. , Tompkins D. , Wilcox M. H.
Published: August 2006

We prospectively studied the comparative epidemiology and risk factors for
Clostridium difficile
,
Clostridium perfringens
, and
Staphylococcus aureus
antibiotic-associated diarrhea (AAD). Four thousand six hundred fifty-nine inpatient fecal specimens (11 months) were tested for
C. difficile
cytotoxin,
C. perfringens
enterotoxin, and
S. aureus
by Vero cell assay, enzyme-linked immunosorbent assay, and growth on fresh blood agar, respectively. Two distinct age-, sex-, and location-matched control patient groups were used for multivariate logistic regression risk factor analyses: symptomatic patients who were AAD pathogen negative and asymptomatic patients with histories of recent antimicrobial therapy. All AAD pathogen isolates were DNA fingerprinted. In AAD cases, the prevalences of
C. difficile
cytotoxin,
C. perfringens
enterotoxin, and
S. aureus
were 12.7%, 3.3%, and 0.2%, respectively (15.8% overall). Age of >70 years was a common risk factor. Other risk factors for infective AAD and
C. difficile
AAD included length of hospital stay and use of feeding tubes (length of stay odds ratios [OR], 1.017 and 1.012; feeding tube OR, 1.864 and 2.808). Female gender and use of antacids were significantly associated with increased risk of
C. perfringens
AAD (OR, 2.08 and 2.789, respectively), but unlike what was found for
C. difficile
AAD, specific antibiotic classes were not associated with increased risk. A limited number of genotypes caused the majority of
C. difficile
and
C. perfringens
AAD cases. Similar to what was found for
C. difficile
AAD, there was epidemiological evidence of
C. perfringens
AAD case clustering and reinfection due to different strains.
C. difficile
AAD was approximately 4 and 60 times more common than
C. perfringens
AAD and
S. aureus
AAD, respectively. Risk factors for these AAD pathogens differed, highlighting the need to define specific control measures. There is evidence of nosocomial transmission in cases of
C. perfringens
AAD.
Characterization of a Large Outbreak by CTX-M-1-Producing
Klebsiella pneumoniae
and Mechanisms Leading to In Vivo Carbapenem Resistance Development
Authors: Mena Ana , Plasencia Virginia , García Laura , Hidalgo Olga , Ayestarán José Ignacio , Alberti Sebastián , Borrell Nuria , Pérez José L. , Oliver Antonio
Published: August 2006

All extended-spectrum β-lactamase (ESBL)-producing
Enterobacteriaceae
isolates from patients admitted to and adult intensive care unit were prospectively documented from 2002 to 2005, when a large outbreak (51 patients affected) of multiresistant ESBL-producing
Klebsiella pneumoniae
infection was detected. The involvement of a single
K. pneumoniae
clone was demonstrated by pulsed-field gel electrophoresis. In addition to the ESBL-mediated resistance, the epidemic strain uniformly showed cross-resistance to ciprofloxacin, gentamicin, tobramycin, trimethoprim-sulfamethoxazole, and tetracycline, whereas resistance to the β-lactam-β-lactamase inhibitor combinations was variable. The ESBL involved was CTX-M-1, as demonstrated by isoelectric focusing, PCR amplification, and sequencing. CTX-M-1 as well as the aminoglycoside resistance determinants were encoded in a 50-kb plasmid that could be transferred to
Escherichia coli
only by transformation. In two of the infected patients, carbapenem resistance development (MICs of 8 to 12, 16, and >32 μg/ml for imipenem, meropenem, and ertapenem, respectively) was documented, both in clinical samples and in intestinal colonization studies. The analysis of the outer membrane proteins of the carbapenem-susceptible and -resistant isolates revealed that the former expressed only one of the two major porins, OmpK36, whereas the latter did not express either of them. In one of the cases, the lack of expression of OmpK36 was demonstrated to be mediated by the interruption of the coding sequence by the insertion sequence IS
26
. This is the first report of a large outbreak of CTX-M-1-producing
Enterobacteriaceae
and, curiously, the first documented description in the literature of CTX-M-1 in
K. pneumoniae
, despite the fact that this enzyme has been found in multiple species. Furthermore, we document and characterize for the first time carbapenem resistance development in CTX-M-1-producing
Enterobacteriaceae
.
Sensitive, Seminested PCR Amplification of VP1 Sequences for Direct Identification of All Enterovirus Serotypes from Original Clinical Specimens
Authors: Nix W. Allan , Oberste M. Steven , Pallansch Mark A.
Published: August 2006

A reverse transcription-seminested PCR (RT-snPCR) assay was developed for the detection and identification of enterovirus (EV) RNA in clinical specimens. Three conserved protein motifs were identified by aligning the VP3 and VP1 sequences of prototype EV strains. Consensus degenerate primers were designed from a conserved VP3 motif and a distal VP1 motif for the first PCR. Consensus-degenerate hybrid oligonucleotide primers were designed from an internal VP1 motif and used with the same distal VP1 motif for the second, seminested PCR step. The primers were designed for broad target specificity and amplified all recognized and proposed EV serotypes and other antigenic variant strains tested. The VP1 RT-snPCR assay was slightly more sensitive than our in-house EV 5′ nontranslated region RT-snPCR assay, detecting as few as 10 RNA copies per reaction. As an example application, the VP1 RT-snPCR assay was used to identify EVs in clinical specimens. A product of the expected size was successfully amplified and sequenced from cerebrospinal fluid; serum; stool suspensions; and nasopharyngeal, eye, and rectal swab specimens, allowing unambiguous identification of the infecting virus in all cases. The VP1 sequences derived from the RT-snPCR products allow rapid phylogenetic and molecular epidemiologic analysis of strains circulating during the EV season and comparison with EV sequences from past seasons or from different locations around the world.
Bacteremia Caused by
Solobacterium moorei
in a Patient with Acute Proctitis and Carcinoma of the Cervix
Authors: Lau Susanna K. P. , Teng Jade L. L. , Leung Kit-Wah , Li Norris K. H. , Ng Kenneth H. L. , Chau Kam-Yu , Que Tak-Lun , Woo Patrick C. Y. , Yuen Kwok-Yung
Published: August 2006

We describe a case of
Solobacterium moorei
bacteremia in a 43-year-old woman presenting with acute proctitis complicating radiotherapy for cervical carcinoma. Phenotypic tests failed to identify the bacterium, which was subsequently identified by 16S rRNA gene sequencing. 16S rRNA gene sequencing could help better define the pathogenicity of
S. moorei
.
Community-Acquired Meningitis and Sepsis Caused by
Chryseobacterium meningosepticum
in a Patient Diagnosed with Thalassemia Major
Authors: Ozkalay Nisel , Anil Murat , Agus Neval , Helvaci Mehmet , Sirti Seral
Published: August 2006

Chryseobacterium meningosepticum
is a rare pathogen in cases of bacterial meningitis in adults and adolescents. We report on the case history of a 17-year-old boy with thalassemia major and meningitis and sepsis caused by
C. meningosepticum
in splenectomized. The patient received vancomycin therapy for 21 days and was discharged in a state of complete recovery.
Identification of
Histoplasma capsulatum
,
Blastomyces dermatitidis
, and
Coccidioides
Species by Repetitive-Sequence-Based PCR
Authors: Pounder June I. , Hansen Dewey , Woods Gail L.
Published: August 2006

The performance of repetitive-sequence-based PCR (rep-PCR) using the DiversiLab system for identification of
Coccidioides
species,
Blastomyces dermatitidis
, and
Histoplasma capsulatum
was assessed by comparing data obtained to colony morphology and microscopic characteristics and to nucleic acid probe results. DNA from cultures of 23
Coccidioides
, 24
B. dermatitidis
, 24
H. capsulatum
, 3
Arthrographis
, and 2
Malbranchea
isolates was extracted using a microbial DNA isolation kit as recommended by Bacterial Barcodes, Inc. Rep-PCR and probe results agreed for 97.2% of the dimorphic fungi when ≥85% similarity was used as the criterion for identification. Two
H. capsulatum
isolates were not identified, but no isolates were misidentified. From 43 of those cultures (15
Coccidioides
, 14
B. dermatitidis
, 14
H. capsulatum
, 3
Arthrographis
, and 2
Malbranchea
), DNA also was extracted using an IDI lysis kit, a simpler method. Rep-PCR and probe results agreed for 97.7% of the dimorphic fungi when a criterion of ≥90% similarity was used for identification. One
H. capsulatum
isolate could not be identified; no isolates were misidentified. Using ≥85% similarity for identification resulted in one misidentification. These data suggest that the DiversiLab system can be used to identify
Coccidioides
and
B. dermatitidis
and, possibly,
H. capsulatum
isolates.
Genetic Diversity of Competence Gene Loci in Clinical Genotypes of
Streptococcus mutans
Authors: Klein Marlise I. , Bang Sungyon , Flório Flávia M. , Höfling José Francisco , Gonçalves Reginaldo B. , Smith Daniel J. , Mattos-Graner Renata O.
Published: August 2006

The frequencies of 21 competence genes were analyzed in 94 genotypes of
Streptococcus mutans
. These include those of a main regulatory system (
comCDE
), structural, and other regulatory orthologues identified in the genome of strain UA159. PCR and Southern blot analysis revealed that all genes are widespread within the species.
Multicenter Comparison of Nucleic Acid Extraction Methods for Detection of Severe Acute Respiratory Syndrome Coronavirus RNA in Stool Specimens
Authors: Petrich A. , Mahony J. , Chong S. , Broukhanski G. , Gharabaghi F. , Johnson G. , Louie L. , Luinstra K. , Willey B. , Akhaven P. , Chui L. , Jamieson F. , Louie M. , Mazzulli T. , Tellier R. , Smieja M. , Cai W. , Chernesky M. , Richardson S. E.
Published: August 2006

The emergence of a novel coronavirus (CoV) as the cause of severe acute respiratory syndrome (SARS) catalyzed the development of rapid diagnostic tests. Stool samples have been shown to be appropriate for diagnostic testing for SARS CoV, although it has been recognized to be a heterogeneous and difficult sample that contains amplification inhibitors. Limited information on the efficiency of extraction methods for the purification and concentration of SARS CoV RNA from stool samples is available. Our study objectives were to determine the optimal extraction method for SARS CoV RNA detection and to examine the effect of increased specimen volume for the detection of SARS CoV RNA in stool specimens. We conducted a multicenter evaluation of four automated and four manual extraction methods using dilutions of viral lysate in replicate mock stool samples, followed by quantitation of SARS CoV RNA using real-time reverse transcriptase PCR. The sensitivities of the manual methods ranged from 50% to 100%, with the Cortex Biochem Magazorb method, a magnetic bead isolation method, allowing detection of all 12 positive samples. The sensitivities of the automated methods ranged from 75% to 100%. The bioMérieux NucliSens automated extractor and miniMag extraction methods each had a sensitivity of 100%. Examination of the copy numbers detected and the generation of 10-fold dilutions of the extracted material indicated that a number of extraction methods retained inhibitory substances that prevented optimal amplification. Increasing the volume of sample input did improve detection. This information could be useful for the extraction of other RNA viruses from stool samples and demonstrates the need to evaluate extraction methods for different specimen types.
Use of Seroconversion Panels To Estimate Delay in Detection of Anti-Human Immunodeficiency Virus Antibodies by Enzyme-Linked Immunosorbent Assay of Pooled Compared to Singleton Serum Samples
Authors: Novack Lena , Galai Noya , Yaari Arieh , Orgel Mordechai , Shinar Eilat , Sarov Batia
Published: August 2006

The transfusion of unsafe blood worldwide accounts for 5 to 15% of new human immunodeficiency virus (HIV) infections, most of which occur in sub-Saharan Africa. While developed countries now apply PCR testing of pooled samples, some developing countries still do not have universal screening policies. More efficient low-cost procedures for the screening of pooled samples have the potential to encourage mass screening efforts in resource-poor settings. The aim of this study was to estimate the delay in the detection of HIV antibodies in pooled serum samples compared to that in singleton serum samples by enzyme-linked immunosorbent assay (ELISA) and to evaluate the risk of transfusion-transmitted HIV infection during the window period. Serial blood samples obtained from five HIV seroconversion panels were mixed with HIV-seronegative blood samples to create pools of 6, 12, 16, 24, 32, and 48 samples. The delay in detection of the first anti-HIV antibody-positive sample in tests with pooled samples was calculated for each pool size and compared to that obtained by testing of singleton samples and statistically evaluated by a robust log-linear regression analysis. The risk of a false-negative (FN) result caused by dilution was estimated by use of the incidence risk/window period model. The additional risk of transmission related to ELISA screening of pooled samples for HIV did not exceed 9% of the current risk of an FN result (estimated to be 1/1,067,000). The countries with virus prevalence rates in donors of less than 15% are expected to save up to 30% in the number of tests. ELISA screening of pooled samples could be considered in settings where the testing of blood supplies for HIV is not routinely done.
Pyrosequencing as a Rapid Tool for Identification of GES-Type Extended-Spectrum β-Lactamases
Authors: Poirel Laurent , Naas Thierry , Nordmann Patrice
Published: August 2006

A pyrosequencing technique was used for identification of extended-spectrum β-lactamases (ESBLs) of GES type. These β-lactamases are isolated increasingly emerging in gram-negative bacteria worldwide. This rapid and reliable identification method is interesting, since GES variants, including not only expanded-spectrum cephalosporins but also carbapenems, cephamycins, and monobactams, are the only ESBLs that possess different hydrolysis profiles.
Increasing Appearance of Reassortant Influenza B Virus in Taiwan from 2002 to 2005
Authors: Tsai Huey-Pin , Wang Hsuan-Chen , Kiang David , Huang Sheng-Wen , Kuo Pin-Hwa , Liu Ching-Chuan , Su Ih-Jen , Wang Jen-Ren
Published: August 2006

Genetic and antigenic analyses of influenza B virus field strains isolated in Taiwan from 1998 to 2005 were performed. To investigate the molecular evolution of influenza B viruses, sequence analysis of the hemagglutinin (HA1 subunit) and neuraminidase genes was performed. All influenza B viruses isolated between 1998 and 2000 belonged to the B/Yamagata/16/88 lineage. The B/Victoria/2/87 lineage, which was cocirculating with the Yamagata lineage, was identified in Taiwan in March 2001. Concurrently, there was an increasing prevalence of this lineage in many parts of the world, including North America and Europe, during the 2001-2002 season. Since 2002, genetic reassortants of influenza B virus with the Victoria lineage of hemagglutinin and the Yamagata lineage of neuraminidase have been found at a rate of 46%. Therefore, in 2002, at least three sublineages of influenza B virus strains, the B/Shanghai/361/2002-like strain (Yamagata lineage), the B/Hong Kong/330/01-like strain (Victoria lineage), and the B/Hong Kong/1351/02-like strain (B reassortant lineage), were identified in Taiwan. The results showed that genetically distinct lineages can cocirculate in the population and that the reassortment among these strains plays a role in generating the genetic diversity of influenza B viruses. Interestingly, from January to April 2005, B reassortant viruses became dominant (73%) in Taiwan, which indicated that a mismatch had occurred between the influenza B vaccine strain recommended for the 2004-2005 season in the Northern hemisphere by the World Health Organization and the epidemic strain.
Chronic vulvovaginal pruritus treated successfully with GnRH analogue
Authors: Banerjee A K , de Chazal R
Published: August 2006

A Medline search shows that this is the first reported case where vulvovaginal pruritus was treated successfully with a GnRH analogue. The report describes a patient with chronic premenstrual vulvovaginal pruritus thought to be attributable to autoimmune progesterone dermatitis.
A systems approach to understanding root development
Authors: Brady Siobhan M. , Benfey Philip N.
Published: August 2006

Systems theory has been applied to process analysis in a variety of scientific disciplines from engineering to evolutionary biology. In the recent postgenomic era, the accumulation of an enormous amount of data gained from a variety of technologies has led to a revisiting of systems theory concepts. This systems biology approach has been integral in understanding a variety of processes in a number of model organisms. This review gives an overview of systems biology approaches, from component identification to modeling of networks. Various features of the root, including its development and the availability of high resolution gene expression data sets that describe root development, make the root amenable to a systems approach. The current status of systems approaches to understanding root development is reviewed.
A new dieback disease of Acacia cyclops in South Africa caused by Pseudolagarobasidium acaciicola sp.nov.
Authors: Wood Alan R. , Ginns J.
Published: August 2006

Acacia cyclops A. Cunn. ex G. Don (Fabaceae, Mimosoideae), originating from Western Australia, is a serious environmental weed in South Africa. A dieback disease of A. cyclops occurring in South Africa is described, and a fungus herein named Psuedolagarobasidium acaciicola Ginns sp.nov. (Basidiomycetes, Polyporales, Hyphodermataceae) was consistently isolated from diseased roots of A. cyclops trees showing early dieback symptoms. Isolates of P. acaciicola caused 100% mortality in pathogenicity screening tests using seedlings of A. cyclops. Saplings of A. cyclops were inoculated with one isolate of P. acaciicola, and all plants were killed within 2–3 months. No control plants died. Psuedolagarobasidium acaciicola was reisolated from all inoculated plants that died. Trees growing in the field were inoculated at two sites on two occasions. Most inoculated trees died within 2 years, whereas no control plants died. Eventually P. acaciicola fruited in vitro and in vivo allowing the basidiomes and cultures to be described. This fungus has potential to be developed as a bioherbicide to aid in the control of this serious environmental weed.
Characterization of programmed cell death in the endosperm cells of tomato seed: two distinct death programs
Authors: DeBono Allan G. , Greenwood John S.
Published: August 2006

Programmed cell death (PCD) is a requisite, genetically controlled process in plants resulting in the death of particular cells and tissues and the recycling of the cellular constituents back to the organism. PCD in the lateral and micropylar endosperm cells during and following germination of tomato ( Solanum lycopersicum L.) seeds was characterized by transmission electron microscopy, by terminal d-UTP nick-end labelling of nuclei, and agarose gel electrophoretic analysis of genomic DNA. Postgerminative cells of lateral and micropylar endosperm displayed morphologies and terminal d-UTP nick-end labelling positive nuclei consistent with PCD. PCD was not detected in the lateral endosperm in the absence of the embryo. The embryo’s effect on promoting lateral endosperm PCD could be substituted with gibberellic acid at 50 μmol/L. Micropylar endosperm cells undergo PCD irrespective of incubation with or without the embryo; gibberellic acid only hastens the onset of PCD morphology. Precursor protease vesicles, novel endoplasmic reticulum derived organelles considered markers of PCD, were observed in postgerminative lateral and micropylar endosperm cells. Internucleosomal laddering was not detected in endospermic DNA. These results suggest that a late postimbibition gibberellic acid linked mechanism promotes PCD in the lateral endosperm, whereas the promotion of PCD in the micropylar endosperm occurs early in, or prior to, imbibition.
The possible role of trehalose in the mycorrhiza helper bacterium effect
Authors: Duponnois Robin , Kisa Marija
Published: August 2006

The main objective of the study was to explore the biological pathway that could explain the stimulating effect of mycorrhiza helper bacteria (MHB) on ectomycorrhizal symbiosis. It has been suggested that the ability of MHBs to stimulate mycelial growth is strongly correlated with their effect on ectomycorrhizal establishment; therefore, the role of organic substrates known to be involved in the hyphosphere and mycorrhizosphere effects of this fungal growth promotion were investigated. Therefore, the bacterial influence on fungal growth was tested using two-compartment dishes. One compartment was filled with a minimal medium (M9 medium) amended with different organic compounds (D-glucosamine, oxalic acid, trehalose, malonic acid, citric acid, carboxy-methyl cellulose, starch, or chitin) and inoculated with a MHB isolate ( Pseudomonas monteilii strain HR13). The other compartment contained fungal plugs of Pisolithus albus isolate IR100. Fungal radial growth was stimulated only when Pseudomonas monteilii was grown on M9 medium + trehalose. This result suggests that trehalose has a role in such bacteria–fungus interactions. However, further research, using other biological models, must be undertaken to identify the role of trehalose in the interactions between MHBs and the fungal symbionts at trophic and genetic levels.
Flexible catch-balancing policies for multispecies individual fishery quotas
Authors: Holland Daniel S , Herrera Guillermo E
Published: August 2006

In multispecies fisheries managed with individual fishery quotas, fishers targeting certain species often have insufficient quota to cover other jointly caught species. New Zealand employs a unique, dual quantityprice system to address this problem. In lieu of acquiring quota, fishers can opt to pay a fee per unit of catch known as deemed value (DV). Although designed primarily to create flexibility in catch balancing for individuals, this system can allow aggregate catches to exceed total allowable catches (TACs). The DV system reduces the likelihood that target species catches are constrained by TACs of bycatch species, but also increases the risk of overexploitation of bycatch species. Using a bioeconomic model, we evaluate the risk and efficiency of alternative DV policies in fisheries with one target and one bycatch species. Our simulations suggest that increasing DVs above ex-vessel price in response to TACs being exceeded can control risk of overexploitation without reducing overall efficiency; however, this does shift rents from owners of target species quota to owners of bycatch species quota.
ESTIMATING THE SHAPE PARAMETER OF THE LOG-LOGISTIC DISTRIBUTION
Authors: CHEN ZHENMIN
Published: August 2006

The log-logistic distribution is a useful distribution in survival analysis. Parameter estimation problems have been discussed by many authors. This paper focuses on the interval estimation for the shape parameter of the log-logistic distribution. Bain and Engelhardt3 gave confidence intervals for the parameters of a logistic distribution based on pivotal quantities formed by maximum likelihood estimators. Chen10 proposed another method for obtaining exact confidence intervals of the shape parameter of the log-logistic distribution. Compared with the existing methods for constructing confidence intervals for the parameters of the log-logistic distribution, the method given in Chen10 is easier to use. In the present paper, the pivotal quantity used in Chen10 is adjusted to improve the performance of statistical analysis. Monte Carlo simulation is conducted to compare the performance of different pivotal quantities. The simulation result shows that the adjusted pivotal quantity has better performance, and then should be recommended to the statistics users.
ATTRIBUTE NOISE DETECTION USING MULTI-RESOLUTION ANALYSIS
Authors: FOLLECO ANDRES , KHOSHGOFTAAR TAGHI
Published: August 2006

The value of knowledge inferred from information databases is critically dependent on the quality of data. The identification of noisy attributes which can easily corrupt and curtail valuable knowledge and information from a dataset can be very helpful to analysts. We present a novel detection method to identify noisy attributes in datasets of software metrics using multi-resolution transformations based on Discrete Wavelet Transforms. The proposed method has been applied to supervised datasets of scientific full-scale data from NASA's Software Metric Data Program (MDP) and to a military command, control, and communications system (CCCS). Empirical results have been favorably compared to those obtained from the robust Pairwise Attribute Noise Detection Algorithm (PANDA) using the same MDP datasets and with mixed results for the CCCS data. All results were verified with several case studies that included injecting known simulated noise into specific attributes with no class noise.
ROLE OF INTERACTION ON NOISE-INDUCED TRANSPORT OF TWO COUPLED PARTICLES IN BROWNIAN RATCHET DEVICES
Authors: RETKUTE RENATA , GLEESON JAMES P.
Published: August 2006

The motion of elastically coupled Brownian particles in ratchet-like potentials has attracted much recent interest due to its application to transport processes in many fields, including models of DNA polymers. We consider the influence of the type of interacting force on the transport of two particles in a one-dimensional flashing ratchet. Our aim is to examine whether the common assumption of elastic coupling captures the important features of ratchet transport when the inter-particle forces are more complex. We compare Lennard-Jones type interaction to the classical case of elastically coupled particles. Numerical simulations agree with analytical formulas for the limiting cases where the coupling is very weak or very strong. Parameter values where the Lennard-Jones force is not well approximated by a linearization of the force about the equilibrium distance are identified.
NEW INSIGHT INTO THE FLUCTUATIONS OF THE MOVING VORTEX LATTICE: NON-GAUSSIAN NOISE AND LÉVY FLIGHTS
Authors: SCOLA J. , PAUTRAT A. , GOUPIL C. , SIMON CH. , DOMENGÈS B. , VILLARD C.
Published: August 2006

We report measurements and analysis of the voltage noise due the to vortex motion, performed in superconducting Niobium micro-bridges. Noise in such small systems exhibits important changes from the behavior commonly reported in macroscopic samples. In the low biasing current regime, the voltage fluctuations are shown to deviate substantially from the Gaussian behavior which is systematically observed at higher currents in the so called flux-flow regime. The responsibility of the spatial inhomogeneities of the critical current in this deviation from Gaussian behavior is emphasized. We also report on the first investigation of the effect of an artificial pinning array on the voltage noise statistics. It is shown that the fluctuations can lose their stationarity, and exhibit a Lévy flight-like behavior.
Living on the Edge of Two Changing Worlds: Forecasting the Responses of Rocky Intertidal Ecosystems to Climate Change
Authors: Helmuth Brian , Mieszkowska Nova , Moore Pippa , Hawkins Stephen J.
Published: August 2006

Long-term monitoring shows that the poleward range edges of intertidal biota have shifted by as much as 50 km per decade, faster than most recorded shifts of terrestrial species. Although most studies have concentrated on species-range edges, recent work emphasizes how modifying factors such as regional differences in the timing of low tide can overwhelm large-scale climatic gradients, leading to a mosaic of environmental stress. We discuss how changes in the mean and variability in climatic regimes, as modified by local and regional factors, can lead to complex patterns of species distribution rather than simple range shifts. We describe how ecological forecasting may be used to generate explicit hypotheses regarding the likely impacts of different climatic change scenarios on the distribution of intertidal species and how related hindcasting methods can be used to evaluate changes that have already been detected. These hypotheses can then be tested over a hierarchy of temporal and spatial scales using coupled field and laboratory-based approaches.
Interstitial cells of Cajal and adaptive relaxation in the mouse stomach
Authors: Dixit Devika , Zarate Natalia , Liu Louis W. C. , Boreham Douglas R. , Huizinga Jan D.
Published: August 2006

Interstitial cells of Cajal (ICC) are proposed to play a role in stretch activation of nerves and are under intense investigation for potential roles in enteric innervation. Most data to support such roles come from in vitro studies with muscle strips whereas data at the whole organ level are scarce. To obtain insight into the role of ICC in distention-induced motor patterns developing at the organ level, we studied distension-induced adaptive relaxation in the isolated whole stomach of wild-type and W/Wv mice. A method was developed to assess gastric adaptive relaxation that gave quantitative information on rates of pressure development and maximal adaptive relaxation. Pressure development was monitored throughout infusion of 1 ml of solution over a 10-min period. The final intraluminal pressure was sensitive to blockade of nitric oxide synthase, in wild-type and W/Wv mice to a similar extent, indicating NO-mediated relaxation in W/Wv mice. Adaptive relaxation occurred between 0.2 and 0.5 ml of solution infusion; this reflex was abolished by TTX, was not sensitive to blockade of nitric oxide synthase, but was abolished by apamin, suggesting that ATP and not nitric oxide is the neurotransmitter responsible for this intrinsic reflex. Despite the absence of intramuscular ICC (ICC-IM), normal gastric adaptive relaxation occurred in the W/Wv stomach. Because pressure development was significantly lower in W/Wv mice compared with wild type in all the conditions studied, including in the presence of TTX, ICC-IM may play a role in development of myogenic tone. In conclusion, a mouse model was developed to assess the intrinsic component of gastric accommodation. This showed that ICC-IM are not essential for activation of intrinsic sensory nerves nor ATP-driven adaptive relaxation nor NO-mediated relaxation in the present model. ICC-IM may be involved in regulation of (distention-induced) myogenic tone.
Contributions of astrocytes and CO to pial arteriolar dilation to glutamate in newborn pigs
Authors: Leffler Charles W. , Parfenova Helena , Fedinec Alexander L. , Basuroy Shyamali , Tcheranova Dilyara
Published: August 2006

Astrocytes can act as intermediaries between neurons and cerebral arterioles to regulate vascular tone in response to neuronal activity. Release of glutamate from presynaptic neurons increases blood flow to match metabolic demands. CO is a gasotransmitter that can be related to neural function and blood flow regulation in the brain. The present study addresses the hypothesis that glutamatergic stimulation promotes perivascular astrocyte CO production and pial arteriolar dilation in the newborn brain. Experiments used anesthetized newborn pigs with closed cranial windows, piglet astrocytes, and cerebrovascular endothelial cells in primary culture and immunocytochemical visualization of astrocytic markers. Pial arterioles and arteries of newborn pigs are ensheathed by astrocytes visualized by glial fibrillary acidic protein staining. Treatment (2 h) of astrocytes in culture with l-2-α-aminoadipic acid (l-AAA), followed by 14 h in toxin free medium, dose-dependently increased cell detachment, suggesting injury. Conversely, 16 h of continuous exposure to l-AAA caused no decrease in endothelial cell attachment. In vivo, topical l-AAA (2 mM, 5 h) disrupted the cortical glia limitans histologically. Such treatment also eliminated pial arteriolar dilation to the astrocyte-dependent dilator ADP and to glutamate but not to isoproterenol or CO. Glutamate stimulated CO production by the brain surface that also was abolished following l-AAA. In contrast, tetrodotoxin blocked dilation to N-methyl-d-aspartate but not to glutamate, isoproterenol, or CO or the glutamate-induced increase in CO. The concurrent loss of CO production and pial arteriolar dilation to glutamate following astrocyte injury suggests astrocytes may employ CO as a gasotransmitter for glutamatergic cerebrovascular dilation.
TNF-α increases tyrosine phosphorylation of vascular endothelial cadherin and opens the paracellular pathway through fyn activation in human lung endothelia
Authors: Angelini Daniel J. , Hyun Sang-Won , Grigoryev Dmitry N. , Garg Pallavi , Gong Ping , Singh Ishwar S. , Passaniti Antonino , Hasday Jeffery D. , Goldblum Simeon E.
Published: August 2006

Tumor necrosis factor (TNF)-α is a key mediator of sepsis-associated multiorgan failure, including the acute respiratory distress syndrome. We examined the role of protein tyrosine phosphorylation in TNF-α-induced pulmonary vascular permeability. Postconfluent human lung microvascular and pulmonary artery endothelial cell (EC) monolayers exposed to human recombinant TNF-α displayed a dose- and time-dependent increase in transendothelial [14C]albumin flux in the absence of EC injury. TNF-α also increased tyrosine phosphorylation of EC proteins, and several substrates were identified as the zonula adherens proteins vascular endothelial (VE)-cadherin, and β-catenin, γ-catenin, and p120 catenin (p120ctn). Prior protein tyrosine kinase (PTK) inhibition protected against the TNF-α effect. TNF-α activated multiple PTKs, including src family PTKs. Prior PTK inhibition with the src-selective agents PP1 and PP2 each protected against ∼60% of the TNF-α-induced increment in [14C]albumin flux. PP2 also blocked TNF-α-induced tyrosine phosphorylation of VE-cadherin, γ-catenin, and p120ctn. To identify which src family kinase(s) was required for TNF-α-induced vascular permeability, small interfering RNA (siRNA) targeting each of the three src family PTKs expressed in human EC, c-src, fyn, and yes, were introduced into the barrier function assay. Only fyn siRNA protected against the TNF-α effect, whereas the c-src and yes siRNAs did not. These combined data suggest that TNF-α regulates the pulmonary vascular endothelial paracellular pathway, in part, through fyn activation.
CD38-deficient mice have reduced airway hyperresponsiveness following IL-13 challenge
Authors: Guedes Alonso G. P. , Paulin Jaime , Rivero-Nava Laura , Kita Hirohito , Lund Frances E. , Kannan Mathur S.
Published: August 2006

The transmembrane glycoprotein CD38 in airway smooth muscle is the source of cyclic-ADP ribose, an intracellular calcium-releasing molecule, and is subject to regulatory effects of cytokines such as interleukin (IL)-13, a cytokine implicated in asthma. We investigated the role of CD38 in airway hyperresponsiveness using a mouse model of IL-13-induced airway disease. Wild-type (WT) and CD38-deficient (CD38KO) mice were intranasally challenged with 5 μg of IL-13 three times on alternate days under isoflurane anesthesia. Lung resistance (RL) in response to inhaled methacholine was measured 24 h after the last challenge in pentobarbital-anesthetized, tracheostomized, and mechanically ventilated mice. Bronchoalveolar cytokines, bronchoalveolar and parenchymal inflammation, and smooth muscle contractility and relaxation using tracheal segments were also evaluated. Changes in methacholine-induced RLwere significantly greater in the WT than in the CD38KO mice following intranasal IL-13 challenges. Airway reactivity after IL-13 exposure, as measured by the slope of the methacholine dose-response curve, was significantly higher in the WT than in the CD38KO mice. The rate of isometric force generation in tracheal segments (e.g., smooth muscle reactivity) was greater in the WT than in the CD38KO mice following incubation with IL-13. IL-13 treatment reduced isoproterenol-induced relaxations to similar magnitudes in tracheal segments obtained from WT and CD38KO mice. Both WT and CD38KO mice developed significant bronchoalveolar and parenchymal inflammation after IL-13 challenges compared with naïve controls. The results indicate that CD38 contributes to airway hyperresponsiveness in lungs exposed to IL-13 at least partly by increasing airway smooth muscle reactivity to contractile agonists.
Induction of kidney injury molecule-1 in homozygous Ren2 rats is attenuated by blockade of the renin-angiotensin system or p38 MAP kinase
Authors: de Borst Martin H. , van Timmeren Mirjan M. , Vaidya Vishal S. , de Boer Rudolf A. , van Dalen Mario B. A. , Kramer Andrea B. , Schuurs Theo A. , Bonventre Joseph V. , Navis Gerjan , van Goor Harry
Published: August 2006

Kidney injury molecule-1 (Kim-1) is associated with ischemic and proteinuric tubular injury; however, whether dysregulation of the renin-angiotensin system (RAS) can also induce Kim-1 is unknown. We studied Kim-1 expression in homozygous Ren2 rats, characterized by renal damage through excessive RAS activation. We also investigated whether antifibrotic treatment (RAS blockade or p38 MAP kinase inhibition) would affect Kim-1 expression. At 7 wk of age, homozygous Ren2 rats received a nonhypotensive dose of candesartan (0.05 mg·kg−1·day−1 sc) or the p38 inhibitor SB-239063 (15 mg·kg−1·day−1 sc) for 4 wk; untreated Ren2 and Sprague-Dawley (SD) rats served as controls. Kim-1 mRNA and protein expression were determined by quantitative PCR and immunohistochemistry, respectively, and related to markers of prefibrotic renal damage. Urinary Kim-1 was measured in 8-wk-old Ren2 and SD rats with and without angiotensin-converting enzyme inhibition (ramipril, 1 mg·kg−1·day−1 in drinking water for 4 wk). Untreated Ren2 rats showed a >20-fold increase in renal Kim-1 mRNA (expressed as Kim-1-to-GAPDH ratio): 75.5 ± 43.6 vs. 3.1 ± 1.0 in SD rats ( P < 0.01). Candesartan and SB-239063 strongly reduced Kim-1 mRNA: 3.1 ± 1.5 ( P < 0.01) and 9.8 ± 4.2 ( P < 0.05), respectively. Kim-1 protein expression in damaged tubules paralleled mRNA expression. Kim-1 expression correlated with renal osteopontin, α-smooth muscle actin, and collagen III expression and with tubulointerstitial fibrosis. Damaged tubular segments expressing activated p38 also expressed Kim-1. Urinary Kim-1 was increased in Ren2 vs. SD (458 ± 70 vs. 27 ± 2 pg/ml, P < 0.01) rats and abolished in Ren2 rats treated with ramipril (33 ± 5 pg/ml, P < 0.01). Kim-1 is associated with development of RAS-mediated renal damage. Antifibrotic treatment through RAS blockade or p38 MAP kinase inhibition reduced Kim-1 in the homozygous Ren2 model.
Cigarette Yields and Human Exposure: A Comparison of Alternative Testing Regimens
Authors: Hammond David , Fong Geoffrey T. , Cummings K. Michael , O'Connor Richard J. , Giovino Gary A. , McNeill Ann
Published: August 2006

Objective: There is general agreement that the testing protocol for measuring cigarette smoke constituents—the International Organization for Standardization regimen—is an inappropriate mechanism for evaluating human exposure. Alternative smoking regimens have been introduced in Canada and Massachusetts; however, these regimens have not been evaluated against human smoking behavior and biomeasures of exposure. The objective of this study was to compare measures of smoke volume and nicotine uptake among human smokers against the puffing variables and nicotine yields generated by five different machine smoking regimens: (a) International Organization for Standardization, (b) Massachusetts, (c) Canadian, (d) a Compensatory regimen, and (e) a Human Mimic regimen.

Methods: Measures of smoke volume and puffing behavior were recorded for 51 smokers who used a portable smoking topography device for three 1-week trials. Measures of salivary cotinine were taken at the completion of each week. The cigarette brands smoked by participants were then machine-smoked under five testing regimens, including a human mimic condition where brands were machine smoked using the puffing behavior recorded from human smokers. The total volume of smoke collected from each cigarette and the nicotine, tar, and carbon monoxide yields were recorded.

Results: None of the four machine smoking regimens adequately reflected Human Mimic Yields of tar, nicotine, and carbon monoxide. In addition, none of the four smoking regimens generated nicotine yields that were associated with actual nicotine uptake in humans.

Conclusions: None of the existing smoking regimens adequately represents human smoking behavior nor do they generate yields associated with human measures of nicotine uptake. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1495–501)
15-Deoxy-Δ12,14-prostaglandin J2 induces death receptor 5 expression through mRNA stabilization independently of PPARγ and potentiates TRAIL-induced apoptosis
Authors: Nakata Susumu , Yoshida Tatsushi , Shiraishi Takumi , Horinaka Mano , Kouhara Junji , Wakada Miki , Sakai Toshiyuki
Published: August 2006

15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), the terminal derivative of the PGJ series, is emerging as a potent antineoplastic agent among cyclopentenone prostaglandins derivatives and also known as the endogenous ligand of peroxisome proliferator-activated receptor γ (PPARγ). On the other hand, death receptor 5 (DR5) is a specific receptor for tumor necrosis factor–related apoptosis-inducing ligand (TRAIL), which is one of the most promising candidates for new cancer therapeutics. Here, we report that 15d-PGJ2 induces DR5 expression at both mRNA and protein levels, resulting in the synergistic sensitization of TRAIL-induced apoptosis in human neoplastic cells, such as Jurkat human leukemia cells or PC3 human prostate cancer cells. 15d-PGJ2 significantly increased DR5 mRNA stability, whereas it did not activate DR5 promoter activity. Synthetic PPARγ agonists, such as pioglitazone or rosiglitazone, did not mimic the DR5-inducing effects of 15d-PGJ2, and a potent PPARγ inhibitor GW9662 failed to block DR5 induction by 15d-PGJ2, suggesting PPARγ-independent mechanisms. Cotreatment with 15d-PGJ2 and TRAIL enhanced the sequential activation of caspase-8, caspase-10, caspase-9, caspase-3, and Bid. DR5/Fc chimera protein, zVAD-fmk pancaspase inhibitor, and caspase-8 inhibitor efficiently blocked the activation of these apoptotic signal mediators and the induction of apoptotic cell death enhanced by cotreatment with 15d-PGJ2 and TRAIL. Moreover, a double-stranded small interfering RNA targeting DR5 gene, which suppressed DR5 up-regulation by 15d-PGJ2, significantly attenuated apoptosis induced by cotreatment with 15d-PGJ2 and TRAIL. These results suggest that 15d-PGJ2 is a potent sensitizer of TRAIL-mediated cancer therapeutics through DR5 up-regulation. [Mol Cancer Ther 2006;5(7):1827–35]
The proteasome inhibitor NPI-0052 is a more effective inducer of apoptosis than bortezomib in lymphocytes from patients with chronic lymphocytic leukemia
Authors: Ruiz Stacey , Krupnik Yelena , Keating Michael , Chandra Joya , Palladino Michael , McConkey David
Published: August 2006

Proteasome inhibitors are potent inducers of apoptosis in isolated lymphocytes from patients with chronic lymphocytic leukemia (CLL). However, the reversible proteasome inhibitor bortezomib (PS-341; Velcade) did not display substantial antitumor activity in CLL patients. Here, we compared the effects of bortezomib and a new irreversible proteasome inhibitor (NPI-0052) on 20S chymotryptic proteasome activity and apoptosis in isolated CLL cells in vitro. Although their steady-state (3 hours) IC50s as proteasome inhibitors were similar, NPI-0052 exerted its effects more rapidly than bortezomib, and drug washout experiments showed that short exposures to NPI-0052 resulted in sustained (≥24 hours) 20S proteasome inhibition, whereas 20S activity recovered in cells exposed to even 10-fold higher concentrations of bortezomib. Thus, brief (15 minutes) pulses of NPI-0052 were sufficient to induce substantial apoptosis in CLL cells, whereas longer exposure times (≥8 hours) were required for commitment to apoptosis in cells exposed to equivalent concentrations of bortezomib. Commitment to apoptosis seemed to be related to caspase-4 activation, in that cells exposed to bortezomib or NPI-0052 could be saved from death by addition of a selective caspase-4 inhibitor up to 8 hours after drug exposure. Our results show that NPI-0052 is a more effective proapoptotic agent than bortezomib in isolated CLL cells and suggest that the chemical properties of NPI-0052 might also make it an effective therapeutic agent in CLL patients. [Mol Cancer Ther 2006;5(7):1836–43]
Pigment epithelium-derived factor: a multimodal tumor inhibitor
Authors: Ek Eugene T.H. , Dass Crispin R. , Choong Peter F.M.
Published: August 2006

Pigment epithelium-derived factor (PEDF), a noninhibitory member of the serine protease inhibitor (serpin) family, is a well-known potent endogenous inhibitor of angiogenesis. It has been known for years to be aberrantly expressed in ocular disorders, but in recent years, down-regulation has been shown to be prevalent in a range of cancers as well. This review describes the trimodal anticancer activities of this interesting protein: antiangiogenesis, apoptosis-mediated tumor suppression, and tumor cell differentiation. The key to successful antitumor therapy with this protein is the ability to synthesize the recombinant form of the protein (or its active shortened forms) and deliver at therapeutic doses or alternatively to use gene transfer technology to prolong the effect in vivo. Although there is a substantial amount of work carried out at the preclinical stage with this protein, more groundwork has to be done before PEDF is tested against cancer in clinical trials. [Mol Cancer Ther 2006;5(7):1641–6]