bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of water regime on archaeal community composition in Arctic soils
Authors: Høj Lone , Rusten Marte , Haugen Lars Egil , Olsen Rolf A. , Torsvik Vigdis L.
Published: January 2006

Effects of water regime on archaeal communities in Arctic soils from Spitsbergen were studied using denaturing gradient gel electrophoresis (DGGE) of amplified 16S rRNA genes, with subsequent sequencing of amplicons and ordination analysis of binary DGGE data. Samples with major differences in soil water regime showed significant differences in their archaeal community profiles. Methanomicrobiales, Methanobacteriaceae and Methanosaeta were detectable only in environments that were wet during most of the growth season, while a novel euryarchaeotal cluster was detected only in less reduced solifluction material. Group 1.3b of Crenarchaeota had a high relative abundance within the archaeal community in a wide range of wet soils. Along a natural soil moisture gradient, changes in archaeal community composition were observed only in upper soil layers. The results indicated that members of Methanomicrobiales were relatively tolerant to soil aeration. Differences in archaeal community composition associated with soil water regime were predominant over regional and seasonal variation, and over differences between individual wetlands. The results suggest that the observed ‘on–off switch’ mechanism of soil hydrology for large‐scale variations in methane emissions from northern wetlands is at least partly caused by differences in the community structure of organisms involved in methane production.
Modelled and measured dynamics of viruses in Arctic winter sea‐ice brines
Authors: Wells Llyd E. , Deming Jody W.
Published: January 2006

We describe a model based on diffusion theory and the temperature‐dependent mechanism of brine concentration in sea ice to argue that, if viruses partition with bacteria into sea‐ice brine inclusions, contact rates between the two can be higher in winter sea ice than in seawater, increasing the probability of infection and possible virus production. To examine this hypothesis, we determined viral and bacterial concentrations in select winter sea‐ice horizons using epifluorescence microscopy. Viral concentrations ranged from 1.6 to 82 × 106 ml−1 of brine volume of the ice, with highest values in brines from coldest (−24 to −31°C) ice horizons. Calculated virus‐bacteria contact rates in underlying −1°C seawater were similar to those in brines of −11°C ice but up to 600 times lower than those in ice brines at or below −24°C. We then incubated native bacterial and viral assemblages from winter sea ice for 8 days in brine at a temperature (−12°C) and salinity (∼160 psu) near expected in situ values, monitoring their concentrations microscopically. While different cores yielded different results, consistent with known spatial heterogeneity in sea ice, these experiments provided unambiguous evidence for viral persistence and production, as well as for bacterial growth, in −12°C brine.
Rapid nitrogen transfer from ectomycorrhizal pines to adjacent ectomycorrhizal and arbuscular mycorrhizal plants in a California oak woodland
Authors: He Xinhua , Bledsoe Caroline S. , Zasoski Robert J. , Southworth Darlene , Horwath William R.
Published: January 2006

Nitrogen transfer among plants in a California oak woodland was examined in a pulse‐labeling study using 15N. The study was designed to examine N movement among plants that were mycorrhizal with ectomycorrhizas (EM), arbuscular mycorrhizas (AM), or both.

Isotopically enriched N (K15NO3−) was applied to gray pine (Pinus sabiniana) foliage (donor) and traced to neighboring gray pine, blue oak (Quercus douglasii), buckbrush (Ceanothus cuneatus) and herbaceous annuals (Cynosurus echinatus, Torilis arvensis and Trifolium hirtum).

After 2 wk, needles of 15N‐treated pines and foliage from nearby annuals were similarly enriched, but little 15N had appeared in nontreated (receiver) pine needles, oak leaves or buckbrush foliage. After 4 wk foliar and root samples from pine, oak, buckbrush and annuals were significantly 15N‐enriched, regardless of the type of mycorrhizal association.

The rate of transfer during the first and second 2‐wk periods was similar, and suggests that 15N could continue to be mobilized over longer times.
Financial behaviours of consumers in credit counselling
Authors: Xiao Jing Jian , Sorhaindo Benoit , Garman E. Thomas
Published: January 2006

Positive financial behaviours of consumers are examined using a national sample of consumers who use credit counselling services in the US from a behavioural economic perspective. The findings indicate that consumers in credit counselling may follow a hierarchical pattern in their financial behaviours, paying off debts and adjusting spending before considering saving. Consumers who are older, have a part‐time job (vs. the unemployed), and report a more secure retirement, a better family relationship, and a higher score of self‐evaluation of financial behaviours are likely to report more positive financial behaviours. Reporting more financial behaviours and a higher score of self‐evaluation of financial behaviours, along with several demographic and perception variables, tend to reduce financial stress and increase financial satisfaction among consumers who use credit counselling services.
An integrative model of consumer satisfaction in the context of e‐services
Authors: Ha Hong‐Youl
Published: January 2006

This research examines how customer satisfaction affects its antecedent and outcome variables such as expectation, performance, disconfirmation, word‐of‐mouth, brand loyalty, attribution and repurchase. This research also takes the important integrative step of understanding the consumer behavioural constructs of consumer satisfaction. Although researchers have focused on the antecedents of consumer satisfaction, our integrative model has extended the outcomes of consumer behaviour on consumer satisfaction. Furthermore, this model strongly suggests a positive view of the inter‐relationships between the antecedent variables and outcome variables of satisfaction. In particular, our model is not consistent with Oliver's attribution models in which satisfaction is a consequence of attribution processing. All hypothesized variables were supported by our empirical study. The findings present a variety of guides to formulating marketing strategies for both practitioners and academics.
Understanding consumers’ perception of clothing quality: a multidimensional approach
Authors: Swinker Mary E. , Hines Jean D.
Published: January 2006

The purpose of this study was to explore how consumers evaluate clothing quality. The researchers used a questionnaire based on responses from previous clothing quality research. It included statements to assess consumers’ use of informational cues to evaluate clothing quality and their expectations of high‐quality garments. A total of 146 students completed the questionnaire. An analysis of the data indicated that 75% of the informational cues and 36% of the expectations of a high‐quality garment were used by the respondents when considering the quality of a garment. The results of this study support the multidimensional nature of consumers’ perception of clothing quality using both informational cues and consumers’ expectations of high‐quality garments.
Reversion of the biochemical defects in murine embryonic Sandhoff neurons using a bicistronic lentiviral vector encoding hexosaminidase α and β
Authors: Arfi Audrey , Zisling Rivka , Richard Emmanuel , Batista Lionel , Poenaru Livia , Futerman Anthony H. , Caillaud Catherine
Published: January 2006

Sandhoff disease, a neurodegenerative disorder characterized by the intracellular accumulation of GM2 ganglioside, is caused by mutations in the hexosaminidase β‐chain gene resulting in a hexosaminidase A (αβ) and B (ββ) deficiency. A bicistronic lentiviral vector encoding both the hexosaminidase α and β chains (SIV.ASB) has previously been shown to correct the β‐hexosaminidase deficiency and to reduce GM2 levels both in transduced and cross‐corrected human Sandhoff fibroblasts. Recent advances in determining the neuropathophysiological mechanisms in Sandhoff disease have shown a mechanistic link between GM2 accumulation, neuronal cell death, reduction of sarcoplasmic/endoplasmic reticulum Ca2+‐ATPase (SERCA) activity, and axonal outgrowth. To examine the ability of the SIV.ASB vector to reverse these pathophysiological events, hippocampal neurons from embryonic Sandhoff mice were transduced with the lentivector. Normal axonal growth rates were restored, as was the rate of Ca2+ uptake via the SERCA and the sensitivity of the neurons to thapsigargin‐induced cell death, concomitant with a decrease in GM2 and GA2 levels. Thus, we have demonstrated that the bicistronic vector can reverse the biochemical defects and down‐stream consequences in Sandhoff neurons, reinforcing its potential for Sandhoff disease in vivo gene therapy.
The Effect of Cuts in Medicare Reimbursement on Hospital Mortality
Authors: Seshamani Meena , Schwartz J. Sanford , Volpp Kevin G.
Published: January 2006

Objective. To determine if patients treated at hospitals under different levels of financial strain from the Balanced Budget Act (BBA) of 1997 had differential changes in 30‐day mortality, and whether vulnerable patient populations such as the uninsured were disproportionately affected.

Data Source. Hospital discharge data from all general acute care hospitals in Pennsylvania from 1997 to 2001.

Study Design. A multivariate regression analysis was performed retrospectively on 30‐day mortality rates, using hospital discharge data, hospital financial data, and death certificate information from Pennsylvania.

Data Collection. We used 370,017 hospital episodes with one of four conditions identified by the Agency for Healthcare Research and Quality as inpatient quality indicators were extracted.

Principal Findings. The average magnitude of Medicare payment reduction on overall net revenues was estimated at 1.8 percent for hospitals with low BBA impact and 3.6 percent for hospitals with a high impact in 1998, worsening to 2 and 4.8 percent, respectively, by 2001. Operating margins decreased significantly over the time period for all hospitals (p<.05). While unadjusted mortality rates demonstrated a disproportionate rise in mortality for patients from high impact hospitals from 1997 to 2000, adjusted analyses show no consistent, significant difference in the rate of change in mortality between high‐impact and low‐impact hospitals (p=.04–.94). Similarly, uninsured patients did not experience greater increases in mortality in high‐impact hospitals relative to low‐impact hospitals.

Conclusions. An analysis of hospitalizations in the Commonwealth of Pennsylvania did not find an adverse impact of increased financial strain from the BBA on patient mortality either among all patients or among the uninsured.
TESTING THE NET BUYING PRESSURE HYPOTHESIS DURING THE ASIAN FINANCIAL CRISIS: EVIDENCE FROM HANG SENG INDEX OPTIONS
Authors: Chan Kam C. , Cheng Louis T. W. , Lung Peter P.
Published: January 2006

We investigate net buying pressure in the Hong Kong Hang Seng Index options market during the Asian financial crisis from July 1997 to August 1998. Our findings suggest that during this period, the dramatic changes in volatility overwhelmed the dynamics of supply and demand in the options market. The extremely high realized volatility drove market participants' expectations about future market volatility in the early months of the crisis. Findings during the late‐crisis, pre‐crisis, and post‐crisis periods are consistent with the net buying pressure hypothesis.
The developmental origins of adult disease (Barker) hypothesis
Authors: DE BOO Hendrina A. , HARDING Jane E.
Published: January 2006

Many studies have provided evidence for the hypothesis that size at birth is related to the risk of developing disease in later life. In particular, links are well established between reduced birthweight and increased risk of coronary heart disease, diabetes, hypertension and stroke in adulthood. These relationships are modified by patterns of postnatal growth. The most widely accepted mechanisms thought to underlie these relationships are those of fetal programming by nutritional stimuli or excess fetal glucocorticoid exposure. It is suggested that the fetus makes physiological adaptations in response to changes in its environment to prepare itself for postnatal life. These changes may include epigenetic modification of gene expression. Less clear at this time are the relevance of fetal programming phenomena to twins and preterm babies, and whether any of these effects can be reversed after birth. Much current active research in this field will be of direct relevance to future obstetric practice.
Placental assessment: Simple techniques to enhance best practice
Authors: KENT Alison L. , DAHLSTROM Jane E.
Published: January 2006

Background:  The placenta provides a ‘diary’ of the pregnancy. The information provided from pathological assessment of the placenta may provide important clinical information for both the mother and the neonate.

Aims:  To develop tools to ensure histopathological assessment of appropriate placentas and uniform provision of clinical history to pathologists to enable clinicopathological assessment.

Methods:  A placenta information form was devised that included the following clinical criteria: gestational age, prolonged rupture of membranes at term, suspected maternal/fetal bacterial or viral infection, swabs taken for culture, intrauterine growth restriction, perinatal death, pre‐eclampsia, essential hypertension, diabetes, placenta praevia, multiple pregnancy and cytogenetics. A table was introduced into the midwifery placenta policy indicating clinical criteria for microbiology, histopathological or cytogenetic assessment. A colourful reminder poster was designed and placed in the delivery suite and education sessions were provided. Six‐month review periods were performed prior to and following the two interventions.

Results:  The number of placentas submitted for histopathological examination (and meeting the inclusion criteria) increased from 41 (120/296) to 61% (161/266) following the initial interventions and to 82% (262/319) with the introduction of the reminder poster and education sessions. Clinically relevant placental pathology was found in 55 (64%) of cases in these time intervals. Comprehensive clinical history on the pathology report improved from 45 to 98% over the assessment time.

Conclusions:  Valuable information on a pregnancy can be provided by ensuring histopathological examination of appropriate placentas with the simple introduction of placental information sheets, updated midwifery policy, education sessions and a colourful reminder poster.
Metabolic Syndrome Predicts Mobility Decline in a Community‐Based Sample of Older Adults
Authors: Blazer Dan G. , Hybels Celia F. , Fillenbaum Gerda G.
Published: January 2006

OBJECTIVES: To determine whether metabolic syndrome is an independent predictor of decline in mobility in an elderly community sample.

DESIGN: Biracial community‐based prospective cohort study.

SETTING: Urban and rural areas of central North Carolina.

PARTICIPANTS: One thousand two hundred twenty‐nine older African Americans and whites, mean age 77.0, who were participants in the Duke Established Populations for Epidemiologic Studies of the Elderly.

MEASUREMENTS: Sociodemographic data and data on mobility (a subset of items from the Rosow‐Breslau scale), depression (Center for Epidemiological Studies Depression Scale), self‐report of medical conditions, body mass index, cognitive function (Short Portable Mental Status Questionnaire), blood pressure, height, and waist circumference. High‐density lipoprotein cholesterol, triglycerides, and blood glucose were available from blood samples. Metabolic syndrome was calculated for subjects with complete data.

RESULTS: Twenty‐nine percent of the sample met criteria for metabolic syndrome. In bivariate analyses, age, sex, race, education, cognitive impairment, depression, impairment in mobility, history of stroke and heart disease, and metabolic syndrome at baseline were associated with a decline in mobility 4 years later. Regression analysis controlling for the above variables demonstrated that metabolic syndrome persisted as an independent and highly significant predictor of decline in mobility.

CONCLUSION: These findings suggest that metabolic syndrome may be a distinct risk factor for mobility decline in community‐dwelling older people.
Funding Faction or Buying Silence? Grants, Contracts, and Interest Group Lobbying Behavior
Authors: Leech Beth L.
Published: January 2006

During the past decade, numerous congressional bills and amendments have attempted to curtail lobbying by nonprofit organizations that receive federal grants. These policy efforts grow out of an assumption that federal funds are encouraging advocacy at levels that are excessive and encourage additional government spending. Using survey data on more than 700 organizations based in Washington, DC, this article tests this assumption. The data show that for the most part, organizations receiving federal grants and contracts lobby no more frequently than similar organizations that do not receive such benefits. The exception is contacting federal agencies, which charitable organizations receiving federal funds do slightly more often than similar organizations without such funds. A multivariate analysis assesses federal funding together with other variables theorized to affect lobbying—federal tax status, resource levels, and the nature of the lobbying issue—confirming that while these other variables affect lobbying levels, federal funding does not.
“Colorblind” Policy in Black and White: Racial Consequences of Disenfranchisement Policy
Authors: Ochs Holona Leanne
Published: January 2006

Disenfranchisement policies were formulated with discriminatory intent in several states (Behrens, Uggen, and Manza 2003;Mauer 2001;Preuhs 2001). Does such discrimination persist? Do disenfranchisement laws disparately impact black voters? I argue that disenfranchisement policies target black citizens and impact black voters disparately compared with white voters. I show that disenfranchisement laws have a disparate impact on the black community that becomes increasingly disproportionate as disenfranchisement laws increase in severity. I find that disenfranchisement policies have a significant independent effect on voting rights in the black community and do not have a similar effect on white voters. I conclude that the ability of the black community to achieve adequate representation is substantially diminished as fewer and fewer blacks qualify for voter registration.
An Integrated Morphological and Molecular Approach to a New Species Description in the Trypanosomatidae: the Case of Leptomonas podlipaevi n. sp., a Parasite of Boisea rubrolineata (Hemiptera: Rhopalidae)
Authors: YURCHENKO VYACHESLAV , LUKEŠ JULIUS , XU XING , MASLOV DMITRI A.
Published: January 2006

ABSTRACT. Leptomonas podlipaevi n. sp., a new trypanosomatid species, is described herein based on light microscopic, ultrastructural, and molecular phylogenetic data. The organism is pleomorphic both in host and culture, with two predominant forms—a typical promastigote with a long flagellum and a shorter promastigote with a small or barely extending flagellum. Several spliced leader RNA repeat sequences obtained from the original cultures and the clonal lines representing two types of cells were all nearly identical. These sequences formed a tight cluster in the neighbor‐joining tree well separated from other trypanosomatid species. Glyceraldehyde phosphate dehydrogenase gene sequences were determined for L. podlipaevi and 10 previously described trypanosomatid species. Molecular phylogenetic analysis has demonstrated that the new species is most closely related to Leptomonas seymouri and Leptomonas pyrrhocoris. The analysis has also highlighted the polyphyly of the genus Leptomonas.
Identification of Three Distinct Polytomella Lineages Based on Mitochondrial DNA Features
Authors: MALLET MARTIN A. , LEE ROBERT W.
Published: January 2006

ABSTRACT. Polytomella is composed of colorless green algae closely related to Chlamydomonas reinhardtii. Species in the genus have been used in diverse fields of biological research, most recently to study mitochondrial function and mitochondrial genome evolution in the Chlorophyceae, but the phylogenetic relationship between the various available taxa has not yet been clarified and it is not known whether they also possess fragmented mitochondrial genomes, as reported for Polytomella parva. We therefore examined cox1 sequence from seven Polytomella taxa with the goal of establishing their phylogenetic relationships and relating this information to their mitochondrial DNA (mtDNA) fragmentation pattern. We found that the Polytomella isolates examined fall into three distinct lineages, two of which possess fragmented mitochondrial genomes. The third and earliest branching lineage, represented by Polytomella capuana, appears to possess an intact mtDNA. In addition, there is evidence for variation in both size and number of mtDNA fragments between various Polytomella isolates, even within the same lineage. The considerable amount of sequence divergence between lineages seems to correlate with the geographic origin of the strains, leading us to believe that greater amounts of sequence divergence could be uncovered by a broader sampling of Polytomella.
Synthesis, antioxidant activity and structure–activity relationships for a new series of 2‐(N‐acylaminoethyl)indoles with melatonin‐like cytoprotective activity
Authors: Spadoni Gilberto , Diamantini Giuseppe , Bedini Annalida , Tarzia Giorgio , Vacondio Federica , Silva Claudia , Rivara Mirko , Mor Marco , Plazzi Pier Vincenzo , Zusso Morena , Franceschini Davide , Giusti Pietro
Published: January 2006

Abstract:  5‐Methoxy‐2‐(N‐acetylaminoethyl)indole (5d), a melatonin analogue derived from the transposition of the acetylaminoethyl side chain from C3 to C2 of the indole nucleus, had been previously characterized as a low affinity antagonist at MT1 and MT2 membrane receptors; this molecule is endowed with good in vitro antioxidant and cytoprotective potency in rat cerebellar cell cultures, comparable to or better than those of melatonin. In order to further investigate the role of structure–antioxidant activity relationships in cytoprotection, the structure of 5d was systematically modulated to design a new series of compounds. The 5‐methoxy group was replaced by substituents with different electronic and lipophilic properties and it was moved to a different position on the indole ring. Other modifications of the lead structure involved the methylation of the indole nitrogen or its replacement by a sulfur atom. The side chain was also modified either increasing its lipophilicity or introducing an ionisable acid group. The antioxidant activity of this set of compounds was evaluated by the ABTS and conjugated dienes (CD) assays, while their cytoprotection was evaluated against kainate‐induced cytotoxicity in cultured cerebellar neurons. In both antioxidant assays, the shift of the 5‐methoxy group to the 4‐position of the indole nucleus led to the most active radical scavenger (9), more potent than the parent compound and melatonin in the antioxidant tests, but much less effective as a cytoprotectant. Sharp structure–activity relationships were registered for cytoprotection, where the maintenance of the 5‐alkoxy‐2‐(N‐acylaminoethyl)indole scaffold appeared as the key feature to confer both antioxidant and cytoprotective activity to the structure. Some derivatives of the set, however, together with the most potent 5d, maintained a significant antioxidant and cytoprotective effect and could be employed as tools for in vivo pharmacological investigations on neuroprotective efficacy of melatonin‐related indoles.
Inhibitory effect of melatonin on diquat‐induced lipid peroxidation in vivo as assessed by the measurement of F2‐isoprostanes
Authors: Zhang Lifu , Wei Wei , Xu Jingming , Min Fanxin , Wang Limei , Wang Xuebin , Cao Shandong , Tan Dun‐Xian , Qi Wenbo , Reiter Russel J.
Published: January 2006

Abstract:  Melatonin is a powerful antioxidant and free radical scavenger. A large body of in vivo and in vitro evidence shows that melatonin effectively inhibits membrane lipid peroxidation; this damage was based on the measurement of malondialdehyde and/or 4‐hydroxynonenal levels. In the current study, for the first time using a more sensitive and specific biomarker, i.e. F2‐isoprostanes, we investigate the effect of melatonin on diquat‐induced lipid peroxidation in Fischer 344 rats. When diquat (40 mg/kg body weight) was intraperitoneally injected into rats, the levels of liver F2‐isoprostanes were significantly increased at 1, 3, and 6 hr while plasma free F2‐isoprostanes concentrations were augmented at 3, 6, and 12 hr after administration of the toxin. In addition, the plasma alanine aminotransferase activity level was measured as a parameter of hepatoxicity; the activity of this enzyme was augmented at 3, 6, and 12 hr after diquat administration when compared with levels of this constituent in untreated control rats. Pretreatment with melatonin (20 mg/kg) 30 min before diquat administration resulted in a significant reduction in both tissue and plasma F2‐isoprostanes levels, and plasma alanine aminotransferase activity. These findings, using a sensitive and specific index of lipid peroxidation, show that the hepatoxicity of diquat, at least partially, is a consequence of reactive oxygen species‐induced lipid damage. Melatonin's protective effects likely relate to its direct free radical scavenging ability and/or due to other antioxidative processes induced by the indole.
Australian baby boomers’ expectations and plans for their old age
Authors: Quine Susan , Carter Stacy
Published: January 2006

The ageing of Australia's 5.5 million baby boomers (born 1946–1965) will significantly change Australian society, yet it is unclear what is known about the expectations and plans of this cohort for their retirement and old age. This paper provides a first step by reviewing the Australian literature, focusing on the areas of health, housing, work and income, and responsibility. Information from the peer‐reviewed literature and the Internet published during 1996–2005 was reviewed. One hundred ninety‐five Australian references were retrieved, of which only 94 were relevant. The review identified that, despite agreement about the significance of baby boomer's ageing, empirical work directly addressing the research topics was rare. In particular, there was little coverage of baby boomers’ ascription of responsibility for their welfare in older age. If policies are to be effective, empirical research obtaining information directly from baby boomers is required to fill the gaps identified through this review.
The Role of Home Gardens in Promoting Multi‐Functional Agriculture in Hungary
Authors: Birol Ekin , Bela Györgyi , Smale Melinda
Published: January 2006

Home gardens are small‐scale family farms managed with traditional methods. Throughout Hungary's history, they have provided food security and diet quality to families who have faced volatile food prices and fluctuating real incomes. If markets function better with European Union (EU) accession, the conditions for reliance on home gardens may weaken—although not for all Hungarians. This paper reports the results of an interdisciplinary project investigating the economic value of home gardens of over 400 farmers in rural Hungary. We find that home gardens generate several public goods, including agro biodiversity and cultural heritage. The most economically, geographically and ecologically marginalized farmers not only manage the home gardens with the highest levels of public goods, but also derive the highest private benefits from them. Should Hungary seek to promote multi functional agriculture in line with the objectives of the EU's reformed Common Agricultural Policy, then provisions for home gardens would need to be incorporated into national programmes and legal frameworks. This research identifies some of the crops and the characteristics of farmers and farming communities that would constitute least cost targets for related programmes. Findings have implications for other EU member Central and Eastern European Countries with similar traditions of home gardening.
Effect of Amphotericin B and Micafungin Combination on Survival, Histopathology, and Fungal Burden in Experimental Aspergillosis in the p47

phox

−
/
−
Mouse Model of Chronic Granulomatous Disease
Authors: Dennis Carly G. , Greco William R. , Brun Yseult , Youn Richard , Slocum Harry K. , Bernacki Ralph J. , Lewis Russell , Wiederhold Nathan , Holland Steven M. , Petraitiene Ruta , Walsh Thomas J. , Segal Brahm H.
Published: January 2006

Chronic granulomatous disease (CGD) is an inherited disorder of the NADPH oxidase characterized by recurrent life-threatening bacterial and fungal infections. We characterized the effects of single and combination antifungal therapy on survival, histopathology, and laboratory markers of fungal burden in experimental aspergillosis in the p47

phox

−
/
−
knockout mouse model of CGD. CGD mice were highly susceptible to intratracheal
Aspergillus fumigatus
challenge, whereas wild-type mice were resistant. CGD mice were challenged intratracheally with a lethal inoculum (1.25 × 10
4
CFU/mouse) of
A. fumigatus
and received one of the following regimens daily from day 0 to 4 after challenge (
n
= 19 to 20 per treatment group): (i) vehicle, (ii) amphotericin B (intraperitoneal; 1 mg/kg of body weight), (iii) micafungin (intravenous; 10 mg/kg), or (iv) amphotericin B plus micafungin. The rank order of therapeutic efficacy based on prolonged survival, from highest to lowest, was as follows: amphotericin B plus micafungin, amphotericin B alone, micafungin alone, and the vehicle. Lung histology showed pyogranulomatous lesions and invasive hyphae, but without hyphal angioinvasion or coagulative necrosis. Treatment with micafungin alone or combined with amphotericin B produced swelling of invasive hyphae that was not present in mice treated with the vehicle or amphotericin B alone. Assessment of lung fungal burden by quantitative PCR showed no significant difference between treatment groups. Serum galactomannan levels were at background despite documentation of invasive aspergillosis by histology. Our findings showed the superior efficacy of the amphotericin B and micafungin combination compared to either agent alone after
A. fumigatus
challenge and also demonstrated unique features of CGD mice as a model for experimental aspergillosis.
Novel Mechanism of Antibiotic Resistance Originating in Vancomycin-Intermediate
Staphylococcus aureus
Authors: Cui Longzhu , Iwamoto Akira , Lian Jian-Qi , Neoh Hui-min , Maruyama Toshiki , Horikawa Yataro , Hiramatsu Keiichi
Published: January 2006

As an aggressive pathogen,
Staphylococcus aureus
poses a significant public health threat and is becoming increasingly resistant to currently available antibiotics, including vancomycin, the drug of last resort for gram-positive bacterial infections.
S. aureus
with intermediate levels of resistance to vancomycin (vancomycin-intermediate
S. aureus
[VISA]) was first identified in 1996. The resistance mechanism of VISA, however, has not yet been clarified. We have previously shown that cell wall thickening is a common feature of VISA, and we have proposed that a thickened cell wall is a phenotypic determinant for vancomycin resistance in VISA (L. Cui, X. Ma, K. Sato, et al., J. Clin. Microbiol.
41:
5-14, 2003). Here we show the occurrence of an anomalous diffusion of vancomycin through the VISA cell wall, which is caused by clogging of the cell wall with vancomycin itself. A series of experiments demonstrates that the thickened cell wall of VISA could protect ongoing peptidoglycan biosynthesis in the cytoplasmic membrane from vancomycin inhibition, allowing the cells to continue producing nascent cell wall peptidoglycan and thus making the cells resistant to vancomycin. We conclude that the cooperative effect of the clogging and cell wall thickening enables VISA to prevent vancomycin from reaching its true target in the cytoplasmic membrane, exhibiting a new class of antibiotic resistance in gram-positive pathogens.
The Two-Component Regulatory System
mtrAB
Is Required for Morphotypic Multidrug Resistance in
Mycobacterium avium
Authors: Cangelosi Gerard A. , Do Julie S. , Freeman Robert , Bennett John G. , Semret Makeda , Behr Marcel A.
Published: January 2006

Clinical isolates of the opportunistic pathogen
Mycobacterium avium
complex (MAC) undergo a reversible switch between red and white colony morphotypes on agar plates containing the lipoprotein stain Congo red. Compared to their isogenic red counterparts, white morphotypic variants are more virulent and more resistant to multiple antibiotics. This report shows that the two-component regulatory system
mtrAB
is required for the red-to-white switch as well as for other morphotypic switches of MAC. A mutant with a transposon insertion in the histidine protein kinase gene
mtrB
was isolated from a morphotypically white parent clone. The mutant resembled a naturally occurring red morphotypic variant in that it stained with Congo red, was sensitive to multiple antibiotics, and was permeable by a fluorescent DNA stain. However, it differed from a red variant in that it could not switch to the white or transparent morphotype, and it could not survive intracellularly within macrophage-like cells. Transcomplementation with a cloned wild-type
mtrB
gene restored to the mutant the ability to form impermeable, drug-resistant white and transparent variants. Quantitative reverse transcriptase PCR showed that
mtrB
was required for the normal expression of cell surface Mce proteins, some of which are up-regulated in the red-to-white switch. The results indicate that
mtrAB
functions in regulating the composition and permeability of mycobacterial cell walls and plays a role in the reversible colony type switches of MAC.
Fluconazole Treatment Is Effective against a
Candida albicans erg3/erg3
Mutant In Vivo Despite In Vitro Resistance
Authors: Miyazaki Taiga , Miyazaki Yoshitsugu , Izumikawa Koichi , Kakeya Hiroshi , Miyakoshi Shunichi , Bennett John E. , Kohno Shigeru
Published: January 2006

Candida albicans ERG3
encodes a sterol C5,6-desaturase which is essential for synthesis of ergosterol. Defective sterol C5,6 desaturation has been considered to be one of the azole resistance mechanisms in this species. However, the clinical relevance of this resistance mechanism is still unclear. In this study, we created a
C. albicans erg3/erg3
mutant by the “Ura-blaster” method and confirmed the expected azole resistance using standard in vitro testing and the presence of ergosta-7,22-dien-3β-ol instead of ergosterol. For in vivo studies, a wild-type
URA3
was placed back into its native locus in the
erg3
homozygote to avoid positional effects on
URA3
expression. Defective hyphal formation of the
erg3
homozygote was observed not only in vitro but in kidney tissues. A marked attenuation of virulence was shown by the longer survival and the lower kidney burdens of mice inoculated with the reconstituted Ura
+
erg3
homozygote relative to the control. To assess fluconazole efficacy in a murine model of disseminated candidiasis, inoculum sizes of the control and the
erg3
homozygote were chosen which provided a similar organ burden. Under these conditions, fluconazole was highly effective in reducing the organ burden in both groups. This study demonstrates that an
ERG3
mutation causing inactivation of sterol C5,6-desaturase cannot confer fluconazole resistance in vivo by itself regardless of resistance measured by standard in vitro testing. The finding questions the clinical significance of this resistance mechanism.
Pharmacokinetics, Safety, and Efficacy of Posaconazole in Patients with Persistent Febrile Neutropenia or Refractory Invasive Fungal Infection
Authors: Ullmann A. J. , Cornely O. A. , Burchardt A. , Hachem R. , Kontoyiannis D. P. , Töpelt K. , Courtney R. , Wexler D. , Krishna G. , Martinho M. , Corcoran G. , Raad I.
Published: January 2006

The pharmacokinetic profiles, safety, and efficacies of different dosing schedules of posaconazole oral suspension in patients with possible, probable, and proven refractory invasive fungal infection (rIFI) or febrile neutropenia (FN) were evaluated in a multicenter, open-label, parallel-group study. Sixty-six patients with FN and 32 patients with rIFI were randomly assigned to one of three posaconazole regimens: 200 mg four times a day (q.i.d.) for nine doses, followed by 400 mg twice a day (b.i.d.); 400 mg q.i.d. for nine doses, followed by 600 mg b.i.d.; or 800 mg b.i.d. for five doses, followed by 800 mg once a day (q.d.). Therapy was continued for up to 6 months in patients with rIFI or until neutrophil recovery occurred in patients with FN. The 400-mg-b.i.d. dose provided the highest overall mean exposure, with 135% (
P
= 0.0004) and 182% (
P
< 0.0001) greater exposure than the 600-mg-b.i.d. and 800-mg-q.d. doses, respectively. However, exposure in allogeneic bone marrow transplant (BMT) recipients (
n
= 12) was 52% lower than in non-BMT patients. Treatment-related adverse events (occurring in 24% of patients) were mostly gastrointestinal in nature. Twenty-four percent of patients had adverse events leading to premature discontinuation (none were treatment related). In efficacy-evaluable patients, successful clinical response was observed in 43% with rIFI (56% of patients receiving 400 mg b.i.d., 17% receiving 600 mg b.i.d., and 50% receiving 800 mg q.d.) and 77% with FN (74% receiving 400 mg b.i.d., 78% receiving 600 mg b.i.d., and 81% receiving 800 mg q.d.). Posaconazole is well tolerated and absorbed. Divided doses of 800 mg (400 mg b.i.d.) provide the greatest posaconazole exposure.
Prediction of the Evolution of Ceftazidime Resistance in Extended-Spectrum β-Lactamase CTX-M-9
Authors: Delmas J. , Robin F. , Carvalho F. , Mongaret C. , Bonnet R.
Published: January 2006

A random mutagenesis technique was used to predict the evolutionary potential of β-lactamase CTX-M-9 toward the acquisition of improved catalytic activity against ceftazidime. Thirty CTX-M mutants were obtained during three rounds of mutagenesis. These mutants conferred 1- to 128-fold-higher MICs of ceftazidime than the parental enzyme CTX-M-9. The CTX-M mutants contained one to six amino acid substitutions. Mutants harbored the substitutions Asp240Gly and Pro167Ser, which were previously observed in clinical CTX-M enzymes. Additional substitutions, notably Arg164His, Asp179Gly, and Arg276Ser, were observed near the active site. The kinetic constants of the three most active mutants revealed two distinct ways of improving catalytic efficiency against ceftazidime. One enzyme had a 17-fold-higher
k
cat
value than CTX-M-9 against ceftazidime. The other two had 75- to 300-fold-lower

K
m

values than CTX-M-9 against ceftazidime. The current emergence of CTX-M β-lactamases with improved activity against ceftazidime may therefore be the beginning of an evolutionary process which might subsequently generate a great diversity of CTX-M-type ceftazidimases.
The social context of smoking: the next frontier in tobacco control?
Authors: Poland B , Frohlich K , Haines R J , Mykhalovskiy E , Rock M , Sparks R
Published: January 2006

A better understanding of the social context of smoking may help to enhance tobacco control research and practice
Medicaid reimbursement for prenatal smoking intervention influences quitting and cessation
Authors: Petersen R , Garrett J M , Melvin C L , Hartmann K E
Published: January 2006

Background:40% of births in the USA are covered by Medicaid and smoking is prevalent among recipients. The objective of this study was to evaluate the association between levels of Medicaid coverage for prenatal smoking cessation interventions on quitting during pregnancy and maintaining cessation after delivery.

Methods:Population based survey study of 7513 post-partum women from 15 states who: participated in Pregnancy Risk Assessment Monitoring System (PRAMS) during 1998–2000; smoked at the beginning of their pregnancy; and had Medicaid coverage. Participating states were categorised into three levels of Medicaid coverage for smoking cessation interventions during prenatal care: extensive (pharmacotherapiesandcounselling); some (pharmacotherapiesorcounselling); or none. Quit rates among women who smoked before pregnancy and rates of maintaining cessation were examined.

Results:Higher levels of coverage during prenatal care for smoking cessation interventions were associated with higher quit rates; 51%, 43%, and 39% of women quit in states with extensive, some, and no coverage, respectively. Compared to women in states with no coverage, women in states with extensive coverage had 1.6 times the odds of quitting smoking (odds ratio (OR) 1.58, 95% confidence interval (CI) 1.00 to 2.49). Maintenance of cessation after delivery was associated with extensive levels of Medicaid coverage; 48% of women maintained cessation in states with extensive coverage compared to 37% of women in states with no coverage. Compared to women in states with no coverage, women with extensive coverage had 1.6 times the odds of maintaining cessation (OR 1.63, 95% CI 1.04 to 2.56).

Conclusions:Prenatal Medicaid coverage for both pharmacotherapiesandcounselling is associated with higher rates of quitting and continued cessation. This suggests policymakers can promote cessation by broadening smoking cessation services in Medicaid prenatal coverage.
Tobacco industry litigation strategies to oppose tobacco control media campaigns
Authors: Ibrahim J K , Glantz Stanton A
Published: January 2006

Objective:To document the tobacco industry’s litigation strategy to impede tobacco control media campaigns.

Methods:Data were collected from news and reports, tobacco industry documents, and interviews with health advocates and media campaign staff.

Results:RJ Reynolds and Lorillard attempted to halt California’s Media Campaign alleging that the campaign polluted jury pools and violated First Amendment rights because they were compelled to pay for anti-industry ads. The American Legacy Foundation was accused of violating the Master Settlement Agreement’s vilification clause because its ads attacked the tobacco industry. The tobacco companies lost these legal challenges.

Conclusion:The tobacco industry has expanded its efforts to oppose tobacco control media campaigns through litigation strategies. While litigation is a part of tobacco industry business, it imposes a financial burden and impediment to media campaigns’ productivity. Tobacco control professionals need to anticipate these challenges and be prepared to defend against them.
VISIBLE PHOTOLUMINESCENCE IN SiCN NANOPARTICLE FILMS GROWN BY PLASMA RF MAGNETRON SPUTTERING
Authors: XU M. , XU S. , NG V. M. , HUANG S. Y. , CHAI J. W. , LONG J. D.
Published: January 2006

SiCN nanoparticle films were prepared by plasma RF magnetron sputtering under a mixture flow of N 2, Ar , and H 2, and optimized in visible photoluminescence (PL) by controlling the N 2 flux. The highest PL intensity was obtained as the N 2 flow rate was set at a moderate value, i.e. 6.4 sccm when the flow rates of Ar and H 2 were 35.2 and 9.6 sccm, respectively. Furthermore, for the sample grown at 400°C, a significant improvement in photoluminescence can be achieved with annealing at 1100°C under N 2 protection, in contrast to that grown at room temperature. The structure and chemical bonding analyzed by X-ray diffraction, X-ray photoelectron spectrum, and Fourier-Transform Infrared spectrum, respectively, revealed that the content of the SiCN nanoparticle, C – N , N – H , and Si – O bonds significantly affect the PL in the SiCN nanoparticle films.
FEW-BODY QUANTUM DYNAMICS IN RELATIVISTIC ION-ATOM COLLISIONS
Authors: VOITKIV A. B.
Published: January 2006

Until recently the theory of relativistic ion-atom collisions was basically restricted to the description of the motion of a single electron in the external field generated by the atomic nucleus and that of the ion-projectile. In the present article we review some of the very recent developments in the theory of relativistic ion-atom collisions which go beyond the single-active-electron picture. Here we discuss processes in which two electrons actively participate and focus our attention in the following two kinds of such processes: (i) double ionization of helium by relativistically moving highly charged nuclei and (ii) two-center dielectronic transitions in relativistic collisions between an atom and an ion.
MILESTONES FOR AUTOMATED REASONING WITH OTTER
Authors: WOS LARRY
Published: January 2006

In the beginning (the early 1960s), the long-term goal of automated reasoning (although the field at the time was not known by that name) was the design and implementation of a program whose use would lead to "real" and significant contributions to mathematics by offering sufficient power for the discovery of proofs. The realization of that goal appeared to be at least six decades in the future. However, with amazement and satisfaction, we can report that fewer than four decades were required. In this article, we present evidence for this claim, thanks to W. McCune's program OTTER. Our focus is on various landmarks, or milestones, of two types. One type concerns the formulation of new strategies and methodologies whose use greatly enhances the power of a reasoning program. A second type focuses on actual contributions to mathematics and (although not initially envisioned) to logic. We give examples of each type of milestone, and, perhaps of equal importance, demonstrate that advances are far more likely to occur if the two classes are closely intertwined. We draw heavily on material presented in great detail in the new book Automated Reasoning and the Discovery of Missing and Elegant Proofs, published by Rinton Press.
Decreased nuclear hormone receptor expression in the livers of mice in late pregnancy
Authors: Sweeney Trevor R. , Moser Arthur H. , Shigenaga Judy K. , Grunfeld Carl , Feingold Kenneth R.
Published: January 2006

During the third trimester of pregnancy, there is an increase in serum triglyceride and cholesterol levels. The mechanisms accounting for these changes in lipid metabolism during pregnancy are unknown. We hypothesized that, during pregnancy, the expression of nuclear hormone receptors involved in regulating lipid metabolism would decrease. In 19-day pregnant mice, serum triglyceride and non-HDL cholesterol levels were significantly increased, whereas total cholesterol was slightly decreased, because of a decrease in the HDL fraction. Peroxisome proliferator-activated receptor (PPAR)α, PPARβ/δ, and PPARγ, liver X receptor (LXR)α and LXRβ, farnesoid X receptor (FXR), and retinoid X receptor (RXR)α, RXRβ, and RXRγ mRNA levels were significantly decreased in the livers of 19-day pregnant mice. Additionally, the expressions of thyroid receptor (TR)α, pregnane X receptor, sterol regulatory element-binding proteins (SREBP)-1a, SREBP-1c, SREBP-2, and liver receptor homolog 1 were also decreased, whereas the expression of TRβ, constitutive androstane receptor, and hepatic nuclear factor 4 showed no significant change. mRNA levels of the PPAR target genes carnitine-palmitoyl transferase 1α and acyl-CoA oxidase, the LXR target genes SREBP1c, ATP-binding cassettes G5 and G8, the FXR target gene SHP, and the TR target genes malic enzyme and Spot14 were all significantly decreased. Finally, the expressions of PPARγ coactivator (PGC)-1α and PGC-1β, known activators of a number of nuclear hormone receptors, were also significantly decreased. The decreases in expression of RXRs, PPARs, LXRs, FXR, TRs, SREBPs, and PGC-1s could contribute to the alterations in lipid metabolism during late pregnancy.