bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal Hemoglobin Inducers from the Natural World: A Novel Approach for Identification of Drugs for the Treatment of β‐Thalassemia and Sickle‐Cell Anemia
Authors: Bianchi Nicoletta , Zuccato Cristina , Lampronti Ilaria , Borgatti Monica , Gambari Roberto
Published: December 2007

The objective of this review is to present examples of lead compounds identified from biological material (fungi, plant extracts and agro‐industry material) and of possible interest in the field of a pharmacological approach to the therapy of β‐thalassemia using molecules able to stimulate production of fetal hemoglobin (HbF) in adults. Concerning the employment of HbF inducers as potential drugs for pharmacological treatment of β‐thalassemia, the following conclusions can be reached: (i) this therapeutic approach is reasonable, on the basis of the clinical parameters exhibited by hereditary persistence of fetal hemoglobin patients, (ii) clinical trials (even if still limited) employing HbF inducers were effective in ameliorating the symptoms of β‐thalassemia patients, (iii) good correlation of in vivo and in vitro results of HbF synthesis and γ‐globin mRNA accumulation indicates that in vitro testing might be predictive of in vivo responses and (iv) combined use of different inducers might be useful to maximize HbF, both in vitro and in vivo. In this review, we present three examples of HbF inducers from the natural world: (i) angelicin and linear psoralens, contained in plant extracts from Angelica arcangelica and Aegle marmelos, (ii) resveratrol, a polyphenol found in grapes and several plant extracts and (iii) rapamycin, isolated from Streptomyces hygroscopicus.
The population genetics of mimetic diversity inHeliconiusbutterflies
Authors: Kronforst Marcus R , Gilbert Lawrence E
Published: December 2007

Theory predicts strong stabilizing selection on warning patterns within species and convergent evolution among species in Müllerian mimicry systems yetHeliconiusbutterflies exhibit extreme wing pattern diversity. One potential explanation for the evolution of this diversity is that genetic drift occasionally allows novel warning patterns to reach the frequency threshold at which they gain protection. This idea is controversial, however, becauseHeliconiusbutterflies are unlikely to experience pronounced population subdivision and local genetic drift. To examine the fine-scale population genetic structure ofHeliconiusbutterflies we genotyped 316 individuals from eight Costa RicanHeliconiusspecies with 1428 AFLP markers. Six species exhibited evidence of population subdivision and/or isolation by distance indicating genetic differentiation among populations. Across species, variation in the extent of local genetic drift correlated with the roles different species have played in generating pattern diversity: species that originally generated the diversity of warning patterns exhibited striking population subdivision while species that later radiated onto these patterns had intermediate levels of genetic diversity and less genetic differentiation among populations. These data reveal thatHeliconiusbutterflies possess the coarse population genetic structure necessary for local populations to experience pronounced genetic drift which, in turn, could explain the origin of mimetic diversity.
Marine worms (genus
Osedax
) colonize cow bones
Authors: Jones William J , Johnson Shannon B , Rouse Greg W , Vrijenhoek Robert C
Published: December 2007

Bone-eating worms of the genus
Osedax
colonized and grew on cow bones deployed at depths ranging from 385 to 2893 m in Monterey Bay, California. Colonization occurred as rapidly as two months following deployment of the cow bones, similar to the time it takes to colonize exposed whalebones. Some
Osedax
females found on the cow bones were producing eggs and some hosted dwarf males in their tubes. Morphological and molecular examinations of these worms confirmed the presence of six
Osedax
species, out of the eight species presently known from Monterey Bay. The ability of
Osedax
species to colonize, grow and reproduce on cow bones challenges previous notions that these worms are ‘whale-fall specialists.’
Category learning induces position invariance of pattern recognition across the visual field
Authors: Jüttner Martin , Rentschler Ingo
Published: December 2007

Human object recognition is considered to be largely invariant to translation across the visual field. However, the origin of this invariance to positional changes has remained elusive, since numerous studies found that the ability to discriminate between visual patterns develops in a largely location-specific manner, with only a limited transfer to novel visual field positions. In order to reconcile these contradicting observations, we traced the acquisition of categories of unfamiliar grey-level patterns within an interleaved learning and testing paradigm that involved either the same or different retinal locations. Our results show that position invariance is an emergent property of category learning. Pattern categories acquired over several hours at a fixed location in either the peripheral or central visual field gradually become accessible at new locations without any position-specific feedback. Furthermore, categories of novel patterns presented in the left hemifield are distinctly faster learnt and better generalized to other locations than those learnt in the right hemifield. Our results suggest that during learning initially position-specific representations of categories based on spatial pattern structure become encoded in a relational, position-invariant format. Such representational shifts may provide a generic mechanism to achieve perceptual invariance in object recognition.
The trade-off between number and size of offspring in humans and other primates
Authors: Walker Robert S , Gurven Michael , Burger Oskar , Hamilton Marcus J
Published: December 2007

Life-history theory posits a fundamental trade-off between number and size of offspring that structures the variability in parental investment across and within species. We investigate this ‘quantity–quality’ trade-off across primates and present evidence that a similar trade-off is also found across natural-fertility human societies. Restating the classic Smith–Fretwell model in terms of allometric scaling of resource supply and offspring investment predicts an inverse scaling relation between birth rate and offspring size and a −¼ power scaling between birth rate and body size. We show that these theoretically predicted relationships, in particular the inverse scaling between number and size of offspring, tend to hold across increasingly finer scales of analyses (i.e. from mammals to primates to apes to humans). The advantage of this approach is that the quantity–quality trade-off in humans is placed into a general framework of parental investment that follows directly from first principles of energetic allocation.
Simultaneous persistence of multiple genome variants of human parvovirus B19
Authors: Schneider Beate , Höne Andrea , Tolba René H. , Fischer Hans-Peter , Blümel Johannes , Eis-Hübinger Anna M.
Published: December 2007

The species human parvovirus B19 (B19V) can be divided into three genotypes. In this study, we addressed the question as to whether infection of an individual is restricted to one genotype. As viral DNA is detectable in tissue for long times after acute infection, we examined 87 liver specimens from adults for the presence of B19V DNA. Fifty-nine samples were found to be positive, 32 of them for genotype 1, 27 for genotype 2 and four for genotype 3. In four samples, DNA of two genotypes was detected; samples from three individuals were positive for genotypes 1 and 2 and a sample from one individual was positive for genotypes 1 and 3. Surprisingly, significant sequence heterogeneity was observed at approximately 1 % of the nucleotides of the genotype 1 genomes from individuals with double genotype 1 and 2 infection. Controls using different enzymes for genome amplification and dilutions of the template verified that nucleotide heterogeneity was due to the presence of three or more genome variants of genotype 1. In summary, the evidence shows that individuals can be infected with two different genotypes, and B19V DNA can persist as a population of different genomes. The results may have implications for the understanding of the antiviral immune response and the development of vaccines against B19V.
CD134 and CXCR4 expression corresponds to feline immunodeficiency virus infection of lymphocytes, macrophages and dendritic cells
Authors: Reggeti F. , Ackerley C. , Bienzle D.
Published: December 2007

The lymphotropic lentiviruses feline immunodeficiency virus (FIV) and human immunodeficiency virus (HIV) enter cells by sequential interaction with primary receptors CD134 or CD4, respectively, and subsequently with chemokine receptors. The host-cell range for FIV is broader than that for HIV, but whether this is a function of receptor expression is unknown. Lack of reagents specific to feline molecules has limited detection and analysis of receptors and their interaction with viral components. Here, the expression of CD134 and CXCR4 on feline T and B lymphocytes, dendritic cells (DCs) and macrophages was examined and the kinetics of FIV replication were assessed. Quantification of CD134 mRNA by real-time PCR indicated expression in all leukocytes, with significantly more transcripts in CD4+lymphocytes than in other leukocytes. Antibodies against human CD134 bound inconsistently to feline leukocytes. CXCR4 was detected with antibody clone 12G5 on the surface of monocyte-derived cells only, but gene transcripts were present in all cells, with the highest copy number in lymphocytes. CXCR4 expression decreased and CD134 expression increased with cell activation in lymphocytes. A subtype B biological isolate of FIV infected DCs, macrophages and lymphocytes, with the highest replication in CD4+lymphocytes, whilst cloned FIV P14 infected all cells, but replicated less efficiently. Although viral replication was lower in DCs and macrophages than in lymphocytes, DCs expressed specific receptors and were infected productively with FIV, as indicated by viral ultrastructure and DNA detection. These results may implicate altered function of DCs in the induction of specific immunity against FIV.
Mechanism of mRNA destabilization by the glmS ribozyme
Authors: Collins Jennifer A. , Irnov Irnov , Baker Stephanie , Winkler Wade C.
Published: December 2007

An array of highly structured domains that function as metabolite-responsive genetic switches has been found to reside within noncoding regions of certain bacterial mRNAs. In response to intracellular fluctuations of their target metabolite ligands, these RNA elements exert control over transcription termination or translation initiation. However, for a particular RNA class within the 5′ untranslated region (UTR) of the glmS gene, binding of glucosamine-6-phosphate stimulates autocatalytic site-specific cleavage near the 5′ of the transcript in vitro, resulting in products with 2′–3′ cyclic phosphate and 5′ hydroxyl termini. The sequence corresponding to this unique natural ribozyme has been subjected to biochemical and structural scrutiny; however, the mechanism by which self-cleavage imparts control over gene expression has yet to be examined. We demonstrate herein that metabolite-induced self-cleavage specifically targets the downstream transcript for intracellular degradation. This degradation pathway relies on action of RNase J1, a widespread ribonuclease that has been proposed to be a functional homolog to the well-studied Escherichia coli RNase E protein. Whereas RNase E only poorly degrades RNA transcripts containing a 5′ hydroxyl group, RNase J1 specifically degrades such transcripts in vivo. These findings elucidate key features of the mechanism for genetic control by a natural ribozyme and suggest that there may be fundamental biochemical differences in RNA degradation machinery between E. coli and other bacteria.
Kinetochore–microtubule interaction during S phase in Saccharomyces cerevisiae
Authors: Kitamura Etsushi , Tanaka Kozo , Kitamura Yoko , Tanaka Tomoyuki U.
Published: December 2007

In the budding yeast Saccharomyces cerevisiae, microtubule-organizing centers called spindle pole bodies (SPBs) are embedded in the nuclear envelope, which remains intact throughout the cell cycle (closed mitosis). Kinetochores are tethered to SPBs by microtubules during most of the cell cycle, including G1 and M phases; however, it has been a topic of debate whether microtubule interaction is constantly maintained or transiently disrupted during chromosome duplication. Here, we show that centromeres are detached from microtubules for 1–2 min and displaced away from a spindle pole in early S phase. These detachment and displacement events are caused by centromere DNA replication, which results in disassembly of kinetochores. Soon afterward, kinetochores are reassembled, leading to their recapture by microtubules. We also show how kinetochores are subsequently transported poleward by microtubules. Our study gives new insights into kinetochore–microtubule interaction and kinetochore duplication during S phase in a closed mitosis.
Dormant origins licensed by excess Mcm2–7 are required for human cells to survive replicative stress
Authors: Ge Xin Quan , Jackson Dean A. , Blow J. Julian
Published: December 2007

In late mitosis and early G1, Mcm2–7 complexes are loaded onto DNA to license replication origins for use in the upcoming S phase. However, the amount of Mcm2–7 loaded is in significant excess over the number of origins normally used. We show here that in human cells, excess chromatin-bound Mcm2–7 license dormant replication origins that do not fire during normal DNA replication, in part due to checkpoint activity. Dormant origins were activated within active replicon clusters if replication fork progression was inhibited, despite the activation of S-phase checkpoints. After lowering levels of chromatin-bound Mcm2–7 in human cells by RNA interference (RNAi), the use of dormant origins was suppressed in response to replicative stress. Although cells with lowered chromatin-bound Mcm2–7 replicated at normal rates, when challenged with replication inhibitors they had dramatically reduced rates of DNA synthesis and reduced viability. These results suggest that the use of dormant origins licensed by excess Mcm2–7 is a new and physiologically important mechanism that cells utilize to maintain DNA replication rates under conditions of replicative stress. We propose that checkpoint kinase activity can preferentially suppress initiation within inactive replicon clusters, thereby directing new initiation events toward active clusters that are experiencing replication problems.
A bacterial metapopulation adapts locally to phage predation despite global dispersal
Authors: Kunin Victor , He Shaomei , Warnecke Falk , Peterson S. Brook , Garcia Martin Hector , Haynes Matthew , Ivanova Natalia , Blackall Linda L. , Breitbart Mya , Rohwer Forest , McMahon Katherine D. , Hugenholtz Philip
Published: December 2007

Using a combination of bacterial and phage-targeted metagenomics, we analyzed two geographically remote sludge bioreactors enriched in a single bacterial speciesCandidatusAccumulibacter phosphatis (CAP). We inferred unrestricted global movement of this species and identified aquatic ecosystems as the primary environmental reservoirs facilitating dispersal. Highly related and geographically remote CAP strains differed principally in genomic regions encoding phage defense mechanisms. We found that CAP populations were high density, clonal, and nonrecombining, providing natural targets for “kill-the-winner” phage predation. Community expression analysis demonstrated that phages were consistently active in the bioreactor community. Genomic signatures linking CAP to past phage exposures were observed mostly between local phage and host. We conclude that CAP strains disperse globally but must adapt to phage predation pressure locally.
Expenditure on healthcare in the UK: A review of the issues
Authors: Propper Carol
Published: December 2007

This review examines the performance of the UK healthcare system. After presenting data on the level and distribution of resources, three topics are examined. The first is the lessons from international comparisons of evidence on expenditure, equity and healthcare outcomes. The second is the lessons from the recent internal market reforms. The third is the lessons from an analysis of the role for private finance in UK healthcare. The review concludes that economists and policymakers need to focus more attention on the relationship between healthcare inputs — expenditure — and health outcomes, and, within this, on the incentives facing suppliers and demanders of healthcare.
The development of competition in the English and Welsh water and sewerage industry
Authors: Sawkins John W.
Published: December 2007

This paper examines the introduction of competition into the English and Welsh water and sewerage industry following privatisation of the 10 regional water authorities in 1989. It outlines the development of comparative, capital and product market competition, arguing that the greatest opportunities now lie with the last through the introduction of common carriage agreements, the extension of Inset appointments and the introduction of transferable abstraction licences. Despite competitive innovations, the industry remains highly regulated, complex and difficult to enter. One of Ofwat's outstanding challenges for the next decade is to examine the means by which the regulatory burden might be lightened and barriers to entry lowered, to encourage potential entrants to compete with incumbents.
Serine-7 of the RNA Polymerase II CTD Is Specifically Required for snRNA Gene Expression
Authors: Egloff Sylvain , O'Reilly Dawn , Chapman Rob D. , Taylor Alice , Tanzhaus Katrin , Pitts Laura , Eick Dirk , Murphy Shona
Published: December 2007

RNA polymerase II (Pol II) transcribes genes that encode proteins and noncoding small nuclear RNAs (snRNAs). The carboxyl-terminal repeat domain (CTD) of the largest subunit of mammalian RNA Pol II, comprising tandem repeats of the heptapeptide consensus Tyr
1
-Ser
2
-Pro
3
-Thr
4
-Ser
5
-Pro
6
-Ser
7
, is required for expression of both gene types. We show that mutation of serine-7 to alanine causes a specific defect in snRNA gene expression. We also present evidence that phosphorylation of serine-7 facilitates interaction with the snRNA gene–specific Integrator complex. These findings assign a biological function to this amino acid and highlight a gene type–specific requirement for a residue within the CTD heptapeptide, supporting the existence of a CTD code.
Accretion of Mudstone Beds from Migrating Floccule Ripples
Authors: Schieber Juergen , Southard John , Thaisen Kevin
Published: December 2007

Mudstones make up the majority of the geological record. However, it is difficult to reconstruct the complex processes of mud deposition in the laboratory, such as the clumping of particles into floccules. Using flume experiments, we have investigated the bedload transport and deposition of clay floccules and find that this occurs at flow velocities that transport and deposit sand. Deposition-prone floccules form over a wide range of experimental conditions, which suggests an underlying universal process. Floccule ripples develop into low-angle foresets and mud beds that appear laminated after postdepositional compaction, but the layers retain signs of floccule ripple bedding that would be detectable in the rock record. Because mudstones were long thought to record low-energy conditions of offshore and deeper water environments, our results call for reevaluation of published interpretations of ancient mudstone successions and derived paleoceanographic conditions.
Habitat Split and the Global Decline of Amphibians
Authors: Becker Carlos Guilherme , Fonseca Carlos Roberto , Haddad Célio Fernando Baptista , Batista Rômulo Fernandes , Prado Paulo Inácio
Published: December 2007

The worldwide decline in amphibians has been attributed to several causes, especially habitat loss and disease. We identified a further factor, namely “habitat split”—defined as human-induced disconnection between habitats used by different life history stages of a species—which forces forest-associated amphibians with aquatic larvae to make risky breeding migrations between suitable aquatic and terrestrial habitats. In the Brazilian Atlantic Forest, we found that habitat split negatively affects the richness of species with aquatic larvae but not the richness of species with terrestrial development (the latter can complete their life cycle inside forest remnants). This mechanism helps to explain why species with aquatic larvae have the highest incidence of population decline. These findings reinforce the need for the conservation and restoration of riparian vegetation.
Mott Transition in VO
2
Revealed by Infrared Spectroscopy and Nano-Imaging
Authors: Qazilbash M. M. , Brehm M. , Chae Byung-Gyu , Ho P.-C. , Andreev G. O. , Kim Bong-Jun , Yun Sun Jin , Balatsky A. V. , Maple M. B. , Keilmann F. , Kim Hyun-Tak , Basov D. N.
Published: December 2007

Electrons in correlated insulators are prevented from conducting by Coulomb repulsion between them. When an insulator-to-metal transition is induced in a correlated insulator by doping or heating, the resulting conducting state can be radically different from that characterized by free electrons in conventional metals. We report on the electronic properties of a prototypical correlated insulator vanadium dioxide in which the metallic state can be induced by increasing temperature. Scanning near-field infrared microscopy allows us to directly image nanoscale metallic puddles that appear at the onset of the insulator-to-metal transition. In combination with far-field infrared spectroscopy, the data reveal the Mott transition with divergent quasi-particle mass in the metallic puddles. The experimental approach used sets the stage for investigations of charge dynamics on the nanoscale in other inhomogeneous correlated electron systems.
Coral Reefs Under Rapid Climate Change and Ocean Acidification
Authors: Hoegh-Guldberg O. , Mumby P. J. , Hooten A. J. , Steneck R. S. , Greenfield P. , Gomez E. , Harvell C. D. , Sale P. F. , Edwards A. J. , Caldeira K. , Knowlton N. , Eakin C. M. , Iglesias-Prieto R. , Muthiga N. , Bradbury R. H. , Dubi A. , Hatziolos M. E.
Published: December 2007

Atmospheric carbon dioxide concentration is expected to exceed 500 parts per million and global temperatures to rise by at least 2°C by 2050 to 2100, values that significantly exceed those of at least the past 420,000 years during which most extant marine organisms evolved. Under conditions expected in the 21st century, global warming and ocean acidification will compromise carbonate accretion, with corals becoming increasingly rare on reef systems. The result will be less diverse reef communities and carbonate reef structures that fail to be maintained. Climate change also exacerbates local stresses from declining water quality and overexploitation of key species, driving reefs increasingly toward the tipping point for functional collapse. This review presents future scenarios for coral reefs that predict increasingly serious consequences for reef-associated fisheries, tourism, coastal protection, and people. As the International Year of the Reef 2008 begins, scaled-up management intervention and decisive action on global emissions are required if the loss of coral-dominated ecosystems is to be avoided.
Risk Factors for Trimethoprim-Sulfamethoxazole Resistance in Patients with Acute Uncomplicated Cystitis
Authors: Colgan Richard , Johnson James R. , Kuskowski Michael , Gupta Kalpana
Published: December 2007

Emerging antimicrobial resistance among uropathogens makes the management of acute uncomplicated cystitis increasingly challenging. Few prospective data are available on the risk factors for resistance to trimethoprim-sulfamethoxazole (TMP-SMX), the drug of choice in most settings. In order to evaluate this, we prospectively enrolled women 18 to 50 years of age presenting to an urban primary care practice with symptoms of cystitis. Potentially eligible women provided a urine sample for culture and completed a questionnaire regarding putative risk factors for TMP-SMX resistance.
Escherichia coli
isolates were tested for clonal group A (CGA) membership by a
fumC
-specific PCR. Of 165 women with cystitis symptoms, 103 had a positive urine culture and were eligible for participation.
E. coli
was the predominant uropathogen (86%). Fifteen (14.6%) women had a TMP-SMX-resistant (TMP-SMX
r
) organism (all of which were
E. coli
). Compared with the women who had a TMP-SMX-susceptible organism, women in the TMP-SMX
r
group were more likely to have traveled (odds ratio [OR], 15.4; 95% confidence interval [CI], 4.4 to 54.3;
P
< 0.001) and to be Asian (OR, 6.1; 95% CI, 1.0 to 36.4;
P
= 0.048). CGA was also independently associated with TMP-SMX resistance (OR, 105; 95% CI, 6.3 to 1,777.6;
P
= 0.001). No association with TMP-SMX resistance was demonstrated for the use of either TMP-SMX or another antibiotic in the past 3 months or with having a child in day care. Among these women with acute uncomplicated cystitis, Asian race and recent travel were independently associated with TMP-SMX resistance. TMP-SMX
r
isolates were more likely to belong to CGA. Knowledge of these risk factors for TMP-SMX resistance could facilitate the accurate selection of empirical therapy.
Molecular and Phenotypic Data Supporting Distinct Species Statuses for
Scedosporium apiospermum
and
Pseudallescheria boydii
and the Proposed New Species
Scedosporium dehoogii
Authors: Gilgado Fèlix , Cano Josep , Gené Josepa , Sutton Deanna A. , Guarro Josep
Published: December 2007

Based on the morphological, physiologic, and molecular (β-tubulin gene) study of 141 isolates of the
Pseudallescheria boydii
species complex (including several synonyms) and relatives, the new species
Scedosporium dehoogii
is proposed.
Scedosporium apiospermum
and
P. boydii
are considered two different species and the new name
Scedosporium boydii
is proposed for the anamorph of the latter species. A summary of the key morphological and physiological features for distinguishing the species of
Pseudallescheria/Scedosporium
is provided.
Comprehensive Study of
Corynebacterium freneyi
Strains and Extended and Emended Description of
Corynebacterium freneyi
Renaud, Aubel, Riegel, Meugnier, and Bollet 2001
Authors: Funke Guido , Frodl Reinhard
Published: December 2007

In 2001,
Corynebacterium freneyi
was described as a new fermentative, α-glucosidase-positive
Corynebacterium
species related to
C. xerosis
based on data from three strains. During a review of our extensive culture collection we encountered 18 additional
C. freneyi
strains and further characterized them in detail. Thirteen of the 18 strains were isolated from female genital tract specimens without any obvious disease association. Phenotypically,
C. freneyi
can be easily differentiated from
C. xerosis
by its distinct wrinkled colonies whereas nearly all other routinely applied phenotypic tests do not allow a unanimous separation of
C. freneyi
from
C. xerosis
. Restriction length polymorphism analysis using CfoI of the 16S-23S rRNA gene intragenic spacer definitively allows differentiation between the two species. Surprisingly, comparative 16S rRNA gene analysis does not discriminate between
C. freneyi
and
C. xerosis
because the designated type strain of
C. freneyi
is not the most representative strain for this species. The present report also includes detailed data on the antimicrobial susceptibility pattern of
C. freneyi
presented here for the first time. Based on the large number of additional
C. freneyi
strains from our culture collection, we provide an extended and emended species description of
C. freneyi
.
Pulsed-Field Gel Electrophoresis ofStaphylococcus aureusIsolates from Atopic Patients Revealing Presence of Similar Strains in Isolates from Children and Their Parents
Authors: Bonness Sonja , Szekat Christiane , Novak Natalija , Bierbaum Gabriele
Published: December 2007

Skin colonization withStaphylococcus aureusis often associated with atopic dermatitis, and staphylococcal enterotoxins have been implicated in the etiology of atopic disease. In this study, the colonization of patients with atopic dermatitis and their parents was investigated in order to evaluate the possibility of intrafamiliar transmission.S. aureusstrains were isolated from 30 of 45 patients (66%). In 19 of 29 families (65%), at least one parent carriedS. aureus, and the overall colonization rate of the parents was 48%. All strains were typed by pulsed-field gel electrophoresis (PFGE), and the presence of enterotoxin genes in the strains was assayed by multiplex PCR. A high percentage (84%) of the isolates present on the children and on at least one of their parents displayed identical PFGE and enterotoxin patterns as well as identical antibiotic resistance profiles, indicating intrafamiliar transmission. Forty-five percent of the strains did not carry any enterotoxin gene. The most frequently found enterotoxin genes weresegandsei, which were present in 36% of the strains, andseb, which was found in 24% of the strains. The other toxin genes occurred only in low frequencies. Most strains were resistant to penicillin (82%), and 15% showed resistance to more than one antibiotic. Intermediately-vancomycin-resistantS. aureusor methicillin-resistantS. aureusstrains were not detected. In conclusion, this study indicates that the colonization rate of parents of atopic children is rather high and may increase the risk of recolonization of the child.
High-Level Fluoroquinolone Resistance in Ophthalmic Clinical Isolates Belonging to the Species
Corynebacterium macginleyi
Authors: Eguchi Hiroshi , Kuwahara Tomomi , Miyamoto Tatsuro , Nakayama-Imaohji Haruyuki , Ichimura Minoru , Hayashi Tetsuya , Shiota Hiroshi
Published: December 2007

The clinical importance of nondiphtherial
Corynebacterium
, a ubiquitous member of the normal human microflora of the skin and mucous membrane, for ocular surface infections has been recognized recently. We performed an antimicrobial susceptibility test with Etest strips for three fluoroquinolones (ciprofloxacin, norfloxacin, and levofloxacin) and a taxonomic analysis on 21 isolates of
Corynebacterium
from ophthalmic samples. Of these, 16 isolates were identified as
C. macginleyi
at the species level on the basis of 16S rRNA gene sequence comparisons. The remaining five isolates were determined to be
C. mastitidis
(four) or
C. accolens
(one). Eleven of the
C. macginleyi
isolates showed high levels of resistance to all of the fluoroquinolones tested, and one isolate was resistant to norfloxacin alone. An analysis of the amplified quinolone-resistance-determining regions of the
gyrA
genes revealed that a single amino acid substitution in position 83 of the
gyrA
product was sufficient to generate the norfloxacin resistance phenotype, and double mutations leading to amino acid changes in positions 83 and 87 were necessary for high-level resistance against the other fluoroquinolones. We conducted the first example of multilocus sequence typing (MLST) analysis on
C. macginleyi
. The MLST analysis grouped the majority of
C. macginleyi
isolates into a single lineage, and another molecular strain typing by random amplified polymorphic DNA fragment patterns supported the finding, indicating that a particular lineage of
C. macginleyi
is dominant on the human ocular surface. This type of population might be particularly adaptable to the milieu on the human ocular surface.
Evaluation of Quantitative Analysis of Cultures from Sonicated Retrieved Orthopedic Implants in Diagnosis of Orthopedic Infection
Authors: Esteban Jaime , Gomez-Barrena Enrique , Cordero Jose , Martín-de-Hijas Nieves Zamora , Kinnari Teemu J. , Fernandez-Roblas Ricardo
Published: December 2007

To improve the microbiological diagnosis of device-related osteoarticular infections, we have developed a protocol based on the sonication of device samples, followed by concentration and inoculation of the sonicate in a broad variety of media in a quantitative manner. Sixty-six samples from 31 patients were included in the study (17 of them with clinical diagnosis of infection). The sonication procedure had a sensitivity of 94.1%, which is better than that of conventional cultures (88.2%). One case of contamination and six cases of unexpected positive cultures were detected (specificity of 42.8%): two of these were considered to represent true infection, while the other four were considered to be nonsignificant (corrected specificity of 50%), although the clinical importance of these isolates is questionable. When we analyzed the number of CFU, no breakpoint between significant and nonsignificant isolates could be established. Based on our results, the procedure of sonication of retrieved implants is better than conventional cultures for the diagnosis of device-related infections. The significance of some isolates in patients without clinical infection remains uncertain. However, they may become pathogens and cannot be routinely considered to be contamination.
Genotypic Characteristics of
Staphylococcus aureus
Isolates from a Multinational Trial of Complicated Skin and Skin Structure Infections
Authors: Campbell Steven J. , Deshmukh Hitesh S. , Nelson Charlotte L. , Bae In-Gyu , Stryjewski Martin E. , Federspiel Jerome J. , Tonthat Giang T. , Rude Thomas H. , Barriere Steven L. , Corey Ralph , Fowler Vance G.
Published: December 2007

The impact of bacterial genetic characteristics on the outcome of patients with
Staphylococcus aureus
infections is uncertain. This investigation evaluated potential associations between bacterial genotype and clinical outcome using isolates collected as part of an international phase 2 clinical trial (FAST II) evaluating telavancin for the treatment of complicated skin and skin structure infections (cSSSI). Ninety
S. aureus
isolates from microbiologically evaluable patients with cSSSI enrolled in the FAST II trial from 11 sites in the United States (56 isolates, or 62%) and 7 sites in South Africa (34 isolates, or 38%) were examined for staphylococcal cassette chromosome
mec
,
agr
, and the presence of 31 virulence genes and subjected to pulsed-field gel electrophoresis (PFGE). South African methicillin-susceptible
S. aureus
(MSSA) isolates were more likely to carry certain virulence genes, including
sdrD
(
P
= 0.01),
sea
(
P
< 0.01), and
pvl
(
P
= 0.01). All 44 (49%) methicillin-resistant
S. aureus
(MRSA) isolates were from the United States; 37 (84%) were strain USA 300 by PFGE. In the United States, MRSA isolates were more likely than MSSA isolates to carry genes for
sdrC
(
P
= 0.03),
map/eap
(
P
= 0.05),
fnbB
(
P
= 0.11),
tst
(
P
= 0.02),
sea
(
P
= 0.04),
sed
(
P
= 0.04),
seg
(
P
= 0.11),
sej
(
P
= 0.11),
agr
(
P
= 0.09),
V8
(
P
= 0.06),
sdrD
,
sdrE
,
eta
,
etb
, and
see
(
P
< 0.01 for all). MRSA isolates were more often clonal than MSSA isolates by PFGE. Isolates from patients who were cured were significantly more likely to contain the
pvl
gene than isolates from patients that failed or had indeterminate outcomes (79/84 [94%] versus 3/6 [50%];
P
= 0.01).
S. aureus
strains from different geographic regions have different distributions of virulence genes.
Identification of
Brachyspira hyodysenteriae
and Other Pathogenic
Brachyspira
Species in Chickens from Laying Flocks with Diarrhea or Reduced Production or Both
Authors: Feberwee Anneke , Hampson David J. , Phillips Nyree D. , La Tom , van der Heijden Harold M. J. F. , Wellenberg Gerard J. , Dwars R. Marius , Landman Wil J. M.
Published: December 2007

Cecal samples from laying chickens from 25 farms with a history of decreased egg production, diarrhea, and/or increased feed conversion ratios were examined for anaerobic intestinal spirochetes of the genus
Brachyspira
. Seventy-three samples positive in an immunofluorescence assay for
Brachyspira
species were further examined using selective anaerobic culture, followed by phenotypic analysis, species-specific PCRs (for
Brachyspira hyodysenteriae
,
B. intermedia
, and
B. pilosicoli
), and a
Brachyspira
genus-specific PCR with sequencing of the partial 16S rRNA gene products.
Brachyspira
cultures were obtained from all samples. Less than half of the isolates could be identified to the species level on the basis of their biochemical phenotypes, while all but four isolates (5.2%) were speciated by using PCR and sequencing of DNA extracted from the bacteria. Different
Brachyspira
spp. were found within a single flock and also in cultures from single chickens, emphasizing the need to obtain multiple samples when investigating outbreaks of avian intestinal spirochetosis. The most commonly detected spirochetes were the pathogenic species
B. intermedia
and
B. pilosicoli
. The presumed nonpathogenic species
B. innocens
,
B. murdochii
, and the proposed “
B. pulli
” also were identified. Pathogenic
B. alvinipulli
was present in two flocks, and this is the first confirmed report of
B. alvinipulli
in chickens outside the United States.
Brachyspira hyodysenteriae
, the agent of swine dysentery, also was identified in samples from three flocks. This is the first confirmed report of natural infection of chickens with
B. hyodysenteriae
. Experimental infection studies are required to assess the pathogenic potential of these
B. hyodysenteriae
isolates.
Candida krusei
, a Multidrug-Resistant Opportunistic Fungal Pathogen: Geographic and Temporal Trends from the ARTEMIS DISK Antifungal Surveillance Program, 2001 to 2005
Authors: Pfaller M. A. , Diekema D. J. , Gibbs D. L. , Newell V. A. , Nagy E. , Dobiasova S. , Rinaldi M. , Barton R. , Veselov A. ,   the Global Antifungal Surveillance Group
Published: December 2007

Candida krusei
is well known as a fungal pathogen for patients with hematologic malignancies and for transplant recipients. Using the ARTEMIS Antifungal Surveillance Program database, we describe geographic and temporal trends in the isolation of
C. krusei
from clinical specimens and the in vitro susceptibilities of 3,448 isolates to voriconazole as determined by CLSI (formerly NCCLS) disk diffusion testing. In addition, we report the in vitro susceptibilities of bloodstream infection isolates of
C. krusei
to amphotericin B (304 isolates), flucytosine (254 isolates), anidulafungin (121 isolates), caspofungin (300 isolates), and micafungin (102 isolates) as determined by CLSI broth microdilution methods. Geographic differences in isolation were apparent; the highest frequency of isolation was seen for the Czech Republic (7.6%) and the lowest for Indonesia, South Korea, and Thailand (0 to 0.3%). Overall, 83% of isolates were susceptible to voriconazole, ranging from 74.8% in Latin America to 92.3% in North America.
C. krusei
was most commonly isolated from hematology-oncology services, where only 76.7% of isolates were susceptible to voriconazole. There was no evidence of increasing resistance of
C. krusei
to voriconazole from 2001 to 2005. Decreased susceptibilities to amphotericin B (MIC at which 90% of isolates were inhibited [MIC
90
], 4 μg/ml) and flucytosine (MIC
90
, 16 μg/ml) were noted, whereas 100% of isolates were inhibited by ≤2 μg/ml of anidulafungin (MIC
90
, 0.06 μg/ml), micafungin (MIC
90
, 0.12 μg/ml) or caspofungin (MIC
90
, 0.25 μg/ml).
C. krusei
is an uncommon but multidrug-resistant fungal pathogen. Among the systemically active antifungal agents, the echinocandins appear to be the most active against this important pathogen.
Human Parechovirus Type 1, 3, 4, 5, and 6 Detection in Picornavirus Cultures
Authors: de Vries Michel , Pyrc Krzysztof , Berkhout Ron , Vermeulen-Oost Wilma , Dijkman Ronald , Jebbink Maarten F. , Bruisten Sylvia , Berkhout Ben , van der Hoek Lia
Published: December 2007

Picornavirus cultures that could not be typed in neutralization assays were analyzed by VP1 reverse transcription-PCR (RT-PCR) and a virus discovery tool (VIDISCA). Human parechoviruses (HPeVs) were frequently identified, among which were the uncommon isolates HPeV-4, HPeV-5, and HPeV-6. The HPeV-5 isolate could be amplified only by VIDISCA and not by VP1 RT-PCR.
Bartonella tamiae
sp. nov., a Newly Recognized Pathogen Isolated from Three Human Patients from Thailand
Authors: Kosoy Michael , Morway Christina , Sheff Kelly W. , Bai Ying , Colborn James , Chalcraft Linda , Dowell Scott F. , Peruski Leonard F. , Maloney Susan A. , Baggett Henry , Sutthirattana Saithip , Sidhirat Anussorn , Maruyama Soichi , Kabeya Hidenori , Chomel Bruno B. , Kasten Rickie , Popov Vsevolod , Robinson Jennilee , Kruglov Alexander , Petersen Lyle R.
Published: December 2007

Three strains of a novel
Bartonella
species (
Bartonella tamiae
) were isolated from human patients from Thailand. Sequence analysis of six chromosomal regions (16S rRNA,
gltA
,
groEL
,
ftsZ
,
rpoB
, and the intergenic spacer region) and phenotypical analysis supported the similarity of the three strains and placed them within the genus
Bartonella
separately from previously described species.
Prevalence and Genetic Diversity of Hepatitis B and Delta Viruses in Pregnant Women in Gabon: Molecular Evidence that Hepatitis Delta Virus Clade 8 Originates from and Is Endemic in Central Africa
Authors: Makuwa Maria , Caron Mélanie , Souquière Sandrine , Malonga-Mouelet Gabriel , Mahé Antoine , Kazanji Mirdad
Published: December 2007

Hepatitis B virus (HBV) surface antigen (HBsAg) was found in 9.2% of 1,186 pregnant women from Gabon, of whom 10.1% had the HBe antigen and 89.9% had anti-HBe antibodies. Antibodies to the hepatitis delta virus (HDV) were found in 15.6% of the HBsAg-positive women. The HBV strains were of the A3 and E genotypes. The HDV strains belonged to HDV clades 1 and 8. These results provide clear evidence that HDV clade 8 is indigenous to Africa.
Difference in Receptor Usage between Severe Acute Respiratory Syndrome (SARS) Coronavirus and SARS-Like Coronavirus of Bat Origin
Authors: Ren Wuze , Qu Xiuxia , Li Wendong , Han Zhenggang , Yu Meng , Zhou Peng , Zhang Shu-Yi , Wang Lin-Fa , Deng Hongkui , Shi Zhengli
Published: December 2007

Severe acute respiratory syndrome (SARS) is caused by the SARS-associated coronavirus (SARS-CoV), which uses angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entry. A group of SARS-like CoVs (SL-CoVs) has been identified in horseshoe bats. SL-CoVs and SARS-CoVs share identical genome organizations and high sequence identities, with the main exception of the N terminus of the spike protein (S), known to be responsible for receptor binding in CoVs. In this study, we investigated the receptor usage of the SL-CoV S by combining a human immunodeficiency virus-based pseudovirus system with cell lines expressing the ACE2 molecules of human, civet, or horseshoe bat. In addition to full-length S of SL-CoV and SARS-CoV, a series of S chimeras was constructed by inserting different sequences of the SARS-CoV S into the SL-CoV S backbone. Several important observations were made from this study. First, the SL-CoV S was unable to use any of the three ACE2 molecules as its receptor. Second, the SARS-CoV S failed to enter cells expressing the bat ACE2. Third, the chimeric S covering the previously defined receptor-binding domain gained its ability to enter cells via human ACE2, albeit with different efficiencies for different constructs. Fourth, a minimal insert region (amino acids 310 to 518) was found to be sufficient to convert the SL-CoV S from non-ACE2 binding to human ACE2 binding, indicating that the SL-CoV S is largely compatible with SARS-CoV S protein both in structure and in function. The significance of these findings in relation to virus origin, virus recombination, and host switching is discussed.
Role of APOBEC3G/F-Mediated Hypermutation in the Control of Human Immunodeficiency Virus Type 1 in Elite Suppressors
Authors: Gandhi Shiv K. , Siliciano Janet D. , Bailey Justin R. , Siliciano Robert F. , Blankson Joel N.
Published: December 2007

While many studies show that the APOBEC3 family of cytidine deaminases can inhibit human immunodeficiency virus type 1 (HIV-1) replication, the clinical significance of this host defense mechanism is unclear. Elite suppressors are HIV-1-infected individuals who maintain viral loads below 50 copies/ml without antiretroviral therapy. To determine the role of APOBEC3G/F proteins in the control of viremia in these patients, we used a novel assay to measure the frequency of hypermutated proviral genomes. In most elite suppressors, the frequency was not significantly different than that observed in patients on highly active antiretroviral therapy. Thus, enhanced APOBEC3 activity alone cannot explain the ability of elite suppressors to control viremia.
Human Immunodeficiency Virus Type 1 Escape Is Restricted When Conserved Genome Sequences Are Targeted by RNA Interference
Authors: von Eije Karin Jasmijn , Brake Olivier ter , Berkhout Ben
Published: December 2007

RNA interference (RNAi) is a cellular mechanism in which small interfering RNAs (siRNAs) mediate sequence-specific gene silencing by cleaving the targeted mRNA. RNAi can be used as an antiviral approach to silence the human immunodeficiency virus type 1 (HIV-1) through stable expression of short-hairpin RNAs (shRNAs). We previously reported efficient HIV-1 inhibition by an shRNA against the nonessential
nef
gene but also described viral escape by mutation or deletion of the
nef
target sequence. The objective of this study was to obtain insight in the viral escape routes when essential and highly conserved sequences are targeted in the Gag, protease, integrase, and Tat-Rev regions of HIV-1. Target sequences were analyzed of more than 500 escape viruses that were selected in T cells expressing individual shRNAs. Viruses acquired single point mutations, occasionally secondary mutations, but—in contrast to what is observed with
nef
—no deletions were detected. Mutations occurred predominantly at target positions 6, 8, 9, 14, and 15, whereas none were selected at positions 1, 2, 5, 18, and 19. We also analyzed the type of mismatch in the siRNA-target RNA duplex, and G-U base pairs were frequently selected. These results provide insight into the sequence requirements for optimal RNAi inhibition. This knowledge on RNAi escape may guide the design and selection of shRNAs for the development of an effective RNAi therapy for HIV-1 infections.