bluuebunny/crossref_metadata_2025 huggingface dataset:
Transport of PIP3 by GAKIN, a kinesin-3 family protein, regulates neuronal cell polarity
Authors: Horiguchi Kaori , Hanada Toshihiko , Fukui Yasuhisa , Chishti Athar H.
Published: July 2006

Phosphatidylinositol-(3,4,5)-trisphosphate (PIP3), a product of phosphatidylinositol 3-kinase, is an important second messenger implicated in signal transduction and membrane transport. In hippocampal neurons, the accumulation of PIP3 at the tip of neurite initiates the axon specification and neuronal polarity formation. We show that guanylate kinase–associated kinesin (GAKIN), a kinesin-like motor protein, directly interacts with a PIP3-interacting protein, PIP3BP, and mediates the transport of PIP3-containing vesicles. Recombinant GAKIN and PIP3BP form a complex on synthetic liposomes containing PIP3 and support the motility of the liposomes along microtubules in vitro. In PC12 cells and cultured hippocampal neurons, transport activity of GAKIN contributes to the accumulation of PIP3 at the tip of neurites. In hippocampal neurons, altered accumulation of PIP3 by overexpression of GAKIN constructs led to the loss of the axonally differentiated neurites. Together, these results suggest that, in neurons, the GAKIN–PIP3BP complex transports PIP3 to the neurite ends and regulates neuronal polarity formation.
Cerebral microcirculation shear stress levels determineNeisseria meningitidisattachment sites along the blood–brain barrier
Authors: Mairey Emilie , Genovesio Auguste , Donnadieu Emmanuel , Bernard Christine , Jaubert Francis , Pinard Elisabeth , Seylaz Jacques , Olivo-Marin Jean-Christophe , Nassif Xavier , Duménil Guillaume
Published: July 2006

Neisseria meningitidis is a commensal bacterium of the human nasopharynx. Occasionally, this bacterium reaches the bloodstream and causes meningitis after crossing the blood–brain barrier by an unknown mechanism. An immunohistological study of a meningococcal sepsis case revealed that neisserial adhesion was restricted to capillaries located in low blood flow regions in the infected organs. This study led to the hypothesis that drag forces encountered by the meningococcus in the bloodstream determine its attachment site in vessels. We therefore investigated the ability of N. meningitidis to bind to endothelial cells in the presence of liquid flow mimicking the bloodstream with a laminar flow chamber. Strikingly, average blood flows reported for various organs strongly inhibited initial adhesion. As cerebral microcirculation is known to be highly heterogeneous, cerebral blood velocity was investigated at the level of individual vessels using intravital imaging of rat brain. In agreement with the histological study, shear stress levels compatible with meningococcal adhesion were only observed in capillaries, which exhibited transient reductions in flow. The flow chamber assay revealed that, after initial attachment, bacteria resisted high blood velocities and even multiplied, forming microcolonies resembling those observed in the septicemia case. These results argue that the combined mechanical properties of neisserial adhesion and blood microcirculation target meningococci to transiently underperfused cerebral capillaries and thus determine disease development.
Development of an Objective Scoring System for Measurement of Resident Performance on the Human Patient Simulator
Authors: Scavone Barbara M. , Sproviero Michele T. , McCarthy Robert J. , Wong Cynthia A. , Sullivan John T. , Siddall Viva J. , Wade Leonard D.
Published: July 2006

Background

The decrease in the percentage of patients having cesarean delivery during general anesthesia has led some educators to advocate the increased use of simulation-based training for this anesthetic. The authors developed a scoring system to measure resident performance of this anesthetic on the human patient simulator and subjected the system to tests of validity and reliability.

Methods

A modified Delphi technique was used to achieve a consensus among several experts regarding a standardized scoring system for evaluating resident performance of general anesthesia for emergency cesarean delivery on the human patient simulator. Eight third-year and eight first-year anesthesiology residents performed the scenario and were videotaped and scored by four attending obstetric anesthesiologists.

Results

Third-year residents scored an average of 150.5 points, whereas first-year residents scored an average of 128 points (P = 0.004). The scoring instrument demonstrated high interrater reliability with an intraclass correlation coefficient of 0.97 (95% confidence interval, 0.94-0.99) compared with the average score.

Conclusions

The developed scoring tool to measure resident performance of general anesthesia for emergency cesarean delivery on the patient simulator seems both valid and reliable in the context in which it was tested. This scoring system may prove useful for future studies such as those investigating the effect of simulator training on objective assessment of resident performance.
Opioid–Volatile Anesthetic Synergy
Authors: Manyam Sandeep C. , Gupta Dhanesh K. , Johnson Ken B. , White Julia L. , Pace Nathan L. , Westenskow Dwayne R. , Egan Talmage D.
Published: July 2006

Background

Combining a hypnotic and an analgesic to produce sedation, analgesia, and surgical immobility required for clinical anesthesia is more common than administration of a volatile anesthetic alone. The aim of this study was to apply response surface methods to characterize the interactions between remifentanil and sevoflurane.

Methods

Sixteen adult volunteers received a target-controlled infusion of remifentanil (0-15 ng/ml) and inhaled sevoflurane (0-6 vol%) at various target concentration pairs. After reaching pseudo-steady state drug levels, the Observer's Assessment of Alertness/Sedation score and response to a series of randomly applied experimental pain stimuli (pressure algometry, electrical tetany, and thermal stimulation) were observed for each target concentration pair. Response surface pharmacodynamic interaction models were built using the pooled data for sedation and analgesic endpoints. Using computer simulation, the pharmacodynamic interaction models were combined with previously reported pharmacokinetic models to identify the combination of remifentanil and sevoflurane that yielded the fastest recovery (Observer's Assessment of Alertness/Sedation score > or = 4) for anesthetics lasting 30-900 min.

Results

Remifentanil synergistically decreased the amount of sevoflurane necessary to produce sedation and analgesia. Simulations revealed that as the duration of the procedure increased, faster recovery was produced by concentration target pairs containing higher amounts of remifentanil. This trend plateaued at a combination of 0.75 vol% sevoflurane and 6.2 ng/ml remifentanil.

Conclusion

Response surface analyses demonstrate a synergistic interaction between remifentanil and sevoflurane for sedation and all analgesic endpoints.
Value of Debriefing during Simulated Crisis Management
Authors: Savoldelli Georges L. , Naik Viren N. , Park Jason , Joo Hwan S. , Chow Roger , Hamstra Stanley J.
Published: July 2006

Background

The debriefing process during simulation-based education has been poorly studied despite its educational importance. Videotape feedback is an adjunct that may enhance the impact of the debriefing and in turn maximize learning. The purpose of this study was to investigate the value of the debriefing process during simulation and to compare the educational efficacy of two types of feedback, oral feedback and videotape-assisted oral feedback, against control (no debriefing).

Methods

Forty-two anesthesia residents were enrolled in the study. After completing a pretest scenario, participants were randomly assigned to receive no debriefing, oral feedback, or videotape-assisted oral feedback. The debriefing focused on nontechnical skills performance guided by crisis resource management principles. Participants were then required to manage a posttest scenario. The videotapes of all performances were later reviewed by two blinded independent assessors who rated participants' nontechnical skills using a validated scoring system.

Results

Participants' nontechnical skills did not improve in the control group, whereas the provision of oral feedback, either assisted or not assisted with videotape review, resulted in significant improvement (P < 0.005). There was no difference in improvement between oral and video-assisted oral feedback groups.

Conclusions

Exposure to a simulated crisis without constructive debriefing by instructors offers little benefit to trainees. The addition of video review did not offer any advantage over oral feedback alone. Valuable simulation training can therefore be achieved even when video technology is not available.
Differential Effects of Volatile Anesthetics on M3Muscarinic Receptor Coupling to the GαqHeterotrimeric G Protein
Authors: Nakayama Tetsuzo , Penheiter Alan R. , Penheiter Sumedha G. , Chini Eduardo N. , Thompson Michael , Warner David O. , Jones Keith A.
Published: July 2006

Background

Halothane inhibits airway smooth muscle contraction in part by inhibiting the functional coupling between muscarinic receptors and one of its cognate heterotrimeric G proteins, Galphaq. Based on previous studies indicating a more potent effect of halothane and sevoflurane on airway smooth muscle contraction compared with isoflurane, the current study hypothesized that at anesthetic concentrations of 2 minimum alveolar concentration (MAC) or less, halothane and sevoflurane but not isoflurane inhibit acetylcholine-promoted Galphaq guanosine nucleotide exchange.

Methods

Galphaq guanosine nucleotide exchange was measured in crude membranes prepared from COS-7 cells transiently coexpressing the human M3 muscarinic receptor and human Galphaq. A radioactive, nonhydrolyzable analog of guanosine-5'-triphosphate, [35S]GTPgammaS, was used as a reporter for nucleotide exchange at Galphaq.

Results

Acetylcholine caused a concentration-dependent increase in Galphaq [35S]GTPgammaS-GDP exchange. Neither anesthetic affected constitutive Galphaq [35S]GTPgammaS-GDP exchange in the absence of acetylcholine. Conversely, each anesthetic caused a concentration-dependent and reversible inhibition of Galphaq [35S]GTPgammaS-GDP exchange when promoted by acetylcholine. At concentrations of 3 MAC or less, the effect of halothane and sevoflurane were significantly greater than that of isoflurane, with only a minimal inhibition by isoflurane observed at 2 MAC.

Conclusion

The differential effects of volatile anesthetics on acetylcholine-promoted guanosine nucleotide exchange at Galphaq are consistent with the apparent more potent direct effect of halothane and sevoflurane compared with isoflurane on muscarinic receptor-mediated contraction of isolated airway smooth muscle. These differential effects also suggest a mode of anesthetic action that could be due to anesthetic-protein interactions and not simply anesthetic accumulation in the lipid membrane.
Anesthesia and Patients with Congenital Hyposensitivity to Pain
Authors: Weingarten Toby N. , Sprung Juraj , Ackerman Joel D. , Bojanic Katarina , Watson James C. , Dyck Peter J.
Published: July 2006

Background

Congenital hyposensitivity to pain or hereditary sensory and autonomic neuropathy represents a variety of disorders characterized by decreased perception of nociception, loss of other modalities of sensation, and variable expression of autonomic dysfunction. Sensory loss, especially that of pain, is associated with self-mutilations that may require frequent operations. Little is known about the safety of anesthesia for these patients.

Methods

The authors performed a computerized search of the Mayo Clinic medical records database between January 1996 and November 2005 for patients with congenital hyposensitivity to pain and related disorders who underwent general anesthesia. Medical records were reviewed for demographics, anesthetic techniques and agents, use of opioids, and perioperative complications. In addition, the authors conducted a comprehensive review of the literature to summarize the current knowledge regarding anesthesia for patients with congenital hyposensitivity to pain, and compared it with the patients with hyposensitivity to pain identified at the Mayo Clinic.

Results

The authors identified seven patients with hereditary sensory and autonomic neuropathy II, IV, or V and undefined variants of congenital pain hyposensitivity who generated 17 anesthesia records: 12 for orthopedic operations, 3 for sural nerve biopsies, and 2 for ophthalmologic procedures. In all patients, standard doses of volatile agents were used during anesthesia. Small amounts of opioids were used during the course of eight operations. Most patients experienced mild hypothermia (lowest temperature 34.7 degrees C), and none experienced hyperthermia. All patients were hemodynamically stable during otherwise uneventful anesthesia. During recovery from anesthesia, opioids were given to only one patient, a single dose of 1 mg morphine. Even after major orthopedic operations, the patient did not require additional analgesia.

Conclusions

The patients with profound congenital hyposensitivity to pain underwent anesthesia without any adverse events. The authors found that despite reduced pain perception, the requirements for volatile anesthetics were within the expected range for population with normal pain perception, but they did not require opioids postoperatively. Intraoperative mild hypothermia was easily managed by adjustment of environmental temperature.
Maternal immunoglobulin concentration in Collared Flycatcher (Ficedula albicollis) eggs in relation to parental quality and laying order
Authors: HARGITAI R. , PRECHL J. , TÖRÖK J.
Published: July 2006

The immune system of newly hatched birds is relatively immature; therefore pathogens can be particularly virulent. Females transfer passive immunity in terms of immunoglobulins to the eggs to protect their young against infections in the crucial early life stages.

As transmission of antibodies is likely to be nutritionally costly, mothers are expected to allocate these components differentially to eggs according to their own condition, the quality of their mate or the laying order of eggs.

We found that in Collared Flycatchers (Ficedula albicollis), yolk antibody levels positively correlated with female body condition, but showed no relationship with maternal age or body size. Furthermore, females with higher plasma heterophil : lymphocyte ratio and heterophil count, which may indicate higher level of stress, deposited lower amount of immunoglobulins to their eggs. These results suggest that females of better physiological condition were able to invest more immunoglobulins to their eggs.

Neither the plumage characteristics, nor the age of the male parent was related to yolk antibody concentration, and thus no evidence for differential allocation of antibodies in relation to male quality or attractiveness could be detected.

Last‐laid eggs contained higher yolk immunoglobulin concentration than earlier‐laid eggs within a clutch. This pattern could be interpreted as a way to improve the survival probability of the disadvantaged last‐hatching nestling.
Environmental sensitivity of sexual size dimorphism: laboratory common garden removes effects of sex and castration on lizard growth
Authors: COX R. M. , ZILBERMAN V. , JOHN‐ALDER H. B.
Published: July 2006

Adult males average 10% larger than females in natural populations of Yarrow's Spiny Lizard (Sceloporus jarrovii). In two previous studies of free‐living animals, we found that (1) this sexual size dimorphism (SSD) develops because yearling males grow more quickly than females and (2) the sex steroid testosterone (T) may regulate this sex difference in growth: castrated males (CAST) grow more slowly than either intact control males (CON) or castrated males treated with exogenous T (TEST).

In the present study, we tested the environmental sensitivity of these sex and treatment effects on growth by raising captive males (CAST, CON, TEST) and females under identical ‘common garden’ conditions.

Sex and treatment effects on growth rate were absent in captivity. The development of SSD was suppressed because captive males grew more slowly than free‐living males of equal size, while experimental treatments failed to affect male growth because CAST grew more quickly in the laboratory common garden than in the field.

Individual growth rates were strongly related to food consumption, but feeding rate did not differ between sexes or among male treatments.

Our results call attention to the environmental sensitivity of sex‐specific endocrine growth regulation and illustrate the importance of combining laboratory and field studies of growth and SSD.
A comparative analysis of contemporary nurses’ discontents
Authors: Forsyth Sue , McKenzie Heather
Published: July 2006

Aim.  This paper reports a study to evaluate and increase understanding of contemporary Registered Nurses’ discontents, and to compare these discontents and their effects with those of nurses 20 years ago.

Background.  In 1986, Turner argued that nurses’ discontents were reflected in a discourse or ‘vocabulary of complaint’ that provided a sense of solidarity amongst practising nurses, and defused their frustrations rather than channelling them into demands for workplace reform. In this paper, we revisit Turner's notion of a vocabulary of complaint in the context of a study of nurse retention in the contemporary Australian healthcare workplace.

Methods.  This paper draws on the qualitative data from a larger project (completed in 2001) exploring the relationship between job satisfaction and self‐concept in both recently graduated and experienced nurses. Here, we elaborate on thematic analyses of the comments of 146 Australian Registered Nurses with more than 5 years’ nursing experience.

Findings.  There is still a high level of discontent amongst contemporary practising nurses, although the focus of their complaints and their responses to them have changed since Turner's study. Conflicting expectations of nurses and managers and lack of opportunity to provide comprehensive care emerged as the most important issues for experienced nurses today. Rather than contributing to a sense of solidarity as in Turner's study, contemporary nurses’ discontents reflect intense personal frustration and underpin individual nurses’ decisions to leave, or plan to leave, the workforce.

Conclusion.  There is an urgent need for increasing health service management and community awareness about the relationship between providing comprehensive nursing care and nurses’ job satisfaction. Addressing nurses’ discontents, wider nursing involvement in the international policy arena, and the politicization of nurses worldwide may contribute to alleviating the current global nursing shortage.
Taking stock of evidence‐based medicine: opportunities for its continuing evolution
Authors: Buetow Stephen , Upshur Ross , Miles Andrew , Loughlin Michael
Published: July 2006

Tough but constructive criticisms of evidence‐based medicine (EBM) have without doubt informed the evolution and serial reconstitutions of this approach to clinical decision making and behaviour. Yet, concerns about EBM persist and as EBM changes in response to reflection and criticism, so too do the criticisms themselves. This paper describes our current understanding of EBM and, to identify opportunities for the continuing evolution of EBM, discusses some key attributes of EBM that still or now cause us concern. Specifically, these attributes are the nature of evidence in EBM; the unknown effectiveness of EBM; the clinician‐centric focus of EBM; and the potential of EBM to harm patients.
The hard art of soft science: Evidence‐Based Medicine, Reasoned Medicine or both?
Authors: Jenicek Milos
Published: July 2006

In the past 14 years, Evidence‐Based Medicine (EBM) has enjoyed unprecedented developments and gained widespread acceptance among health professionals. However, should we be content with producing, critically appraising and using the best evidence available for our understanding of health problems and decision making about them? Are our convictions about EBM’s relevance, our conviction and intellectual satisfaction with its mastery and adoption enough? Should we continue pushing forward along this promising path, or should we further diversify the content and scope of EBM? Is EBM the only way to view medicine in the near future? This paper presents some options to choose from in terms of direction and content as well as questions to answer given the current EBM crossroads. More intensive and extensive EBM combined with ‘other features’‐based medicines may be the preferred strategy to follow in the future to determine the development, use and evaluation of EBM. Argument‐based medicine or Reasoned Medicine is one of the options that can be integrated into the mainstream of medical reasoning and decision making.
Can academic and clinical journals be in financial conflict of interest situations? The case of evidence‐based incorporated
Authors: Upshur Ross , Buetow Stephen , Loughlin Michael , Miles Andrew
Published: July 2006

The hypothesis is advanced that scholarly journals can find themselves in conflict of interest positions when they operate business strategies which for commercial reasons may militate against the publication of articles which question the usefulness of the products being sold. It is suggested on the basis of probabilistic reasoning that the more extensive the merchandizing and the greater the commercial profits, the greater is the potential for conflict of interest. The alternative hypothesis is advanced that such a conflict of interest position cannot possibly exist. The current Hypothesis paper is published in order to stimulate debate on the subject of study. The reader is referred to the Editor’s Note p. 395.
Attachment kinetics of the adult tick Amblyomma variegatum to cattle
Authors: STACHURSKI F.
Published: July 2006

Abstract At the beginning of the 1999 rainy season, three traditional cattle herds were monitored for 48 days while grazing in the bushy savannah of southwestern Burkina Faso. Cattle in each herd were caught on several occasions each day and the attached ticks were counted. This confirmed that Amblyomma variegatum Fabricius (Acari: Ixodidae) adults picked up in the pastures mainly attach to the interdigital areas (87% of the 791 ticks captured), and reach the predilection sites later (chest and udder/inguinal area) when the animals lie down. As many females as males attached to the hosts, but the seasonal distribution was very heterogeneous, with only a few females attaching as long as the humidity rate remained low. It is suggested that this prevents eggs from being laid when conditions are not optimal for their survival and that of the larvae. Ticks attached all day but the number picked up hourly and daily varied greatly according to their density on the pasture. As a general trend, confirmed by another study carried out in 2005, the number of ticks picked up daily increased from less than one tick/animal/day, before the onset of the rainy season, to 6.5 (± 1.5) ticks/animal/day on average during the infestation peak, which lasted 6–8 weeks, until early or mid‐July. The number then decreased to less than one tick/animal/day from the end of July onwards. The infestation on the predilection sites followed the same trend, with a daily tick burden increase of three to five A. variegatum adults, depending on herd and year, during the infestation peak.
Natural selection and climate change: temperature‐linked spatial and temporal trends in gene frequency in Fagus sylvatica
Authors: JUMP ALISTAIR S. , HUNT JENNY M. , MARTÍNEZ‐IZQUIERDO JOSÉ A. , PEÑUELAS JOSEP
Published: July 2006

Rapid increases in global temperature are likely to impose strong directional selection on many plant populations, which must therefore adapt if they are to survive. Within populations, microgeographic genetic differentiation of individuals with respect to climate suggests that some populations may adapt to changing temperatures in the short‐term through rapid changes in gene frequency. We used a genome scan to identify temperature‐related adaptive differentiation of individuals of the tree species Fagus sylvatica. By combining molecular marker and dendrochronological data we assessed spatial and temporal variation in gene frequency at the locus identified as being under selection. We show that gene frequency at this locus varies predictably with temperature. The probability of the presence of the dominant marker allele shows a declining trend over the latter half of the 20th century, in parallel with rising temperatures in the region. Our results show that F. sylvatica populations may show some capacity for an in situ adaptive response to climate change. However as reported ongoing distributional changes demonstrate, this response is not enough to allow all populations of this species to persist in all of their current locations.
Genetic isolation and divergence in sexual traits: evidence for the northern rockhopper penguinEudyptes moseleyibeing a sibling species
Authors: JOUVENTIN P. , CUTHBERT R. J. , OTTVALL R.
Published: July 2006

The taxonomic status of populations of rockhopper penguins (Eudyptes chrysocome) is still enigmatic. Northern populations differ from southern ones in breeding phenology, song characteristics and head ornaments used as mating signals. We conducted a molecular analysis using mitochondrial DNA sequencing to test if there is a gene flow barrier between northern (subtropical) populations and southern (subantarctic) populations in relation to the Subtropical Convergence, a major ecological boundary for marine organisms. Sequences of the control region and the ND2 gene were analysed in rockhopper penguins and in the macaroni penguin (Eudyptes chrysolophus), a closely related species. Genetic distances and phylogenetic analyses showed a clear split into three clades, two rockhopper clades and the macaroni penguin. Moreover, ΘSTand gene flow estimates also suggested genetic structuring within the northern rockhoppers. Our results add further support to the notion that the two rockhopper penguin taxa, often considered as two subspecies, can be recognized as two speciesE. chrysocomeandE. moseleyi. The divergence in mating signals found between these two taxa seems to have occurred recently and relatively rapidly. Thus, the behavioural changes may have been enough to isolate these taxa without the need for morphological differentiation. The findings have important conservational implications, sinceE. moseleyiis far less abundant thanE. chrysocome, but more populations may warrant an uplisting to endangered status if full species status should be recognized for more subpopulations.
Role of a VPS41 homologue in starvation response, intracellular survival and virulence of Cryptococcus neoformans
Authors: Liu Xiaoguang , Hu Guowu , Panepinto John , Williamson Peter R.
Published: July 2006

Previous studies have demonstrated an important role for the vacuole in the virulence of the fungus Cryptococcus and studies in yeast have implicated the vacuolar protein Vps41 in copper loading of proteins such as iron transporters. However, our studies found that a cryptococcal vps41Δ strain displayed wild‐type growth on media containing iron and copper chelators and normal activity of the copper‐containing virulence factor laccase as well as almost normal growth at 37°C and wild‐type production of the virulence factor capsule. Despite these attributes, the vps41Δ mutant strain showed a dramatic attenuation of virulence in mice and co‐incubation of mutant cells with the macrophage cell line, J774.16, resulted in a dramatic loss in viability of the vps41Δ mutant strain at 10 h compared with wild‐type and complemented strains. Closer examination revealed that the vps41Δ mutant displayed a dramatic loss in viability after nutrient starvation which was traced to a failure to undergo G2 arrest, but there was no defect in the formation of autophagic or proteolytic vesicles. Our results indicate that VPS41 plays a key role in regulating starvation response in this pathogenic organism and that defects in cell cycle arrest are associated with attenuated pathogenic fitness in mammalian hosts.
The type III effectors HsvG and HsvB of gall‐forming Pantoea agglomerans determine host specificity and function as transcriptional activators
Authors: Nissan Gal , Manulis‐Sasson Shulamit , Weinthal Dan , Mor Henia , Sessa Guido , Barash Isaac
Published: July 2006

Pantoea agglomerans pv. gypsophilae (Pag) elicits galls on gypsophila and a hypersensitive response on beet, whereas P. agglomerans pv. betae (Pab) induces galls on both beet and gypsophila. The pathogenicity of both pathovars is dependent on the presence of a plasmid harbouring type III secretion system (TTSS) components and effectors. The HsvG TTSS effectors of Pag (HsvG‐Pag) and Pab (HsvG‐Pab) determine the host specificity of both pathovars on gypsophila. Here we describe a novel HsvG homologue, HsvB, which determines the host specificity of Pag and Pab on beet. HsvG requires two direct amino acid repeats for pathogenicity on gypsophila, whereas one repeat in HsvB is sufficient for pathogenicity on beet. Exchanging repeats between HsvG‐Pag and HsvB‐Pab resulted in a switch of host specificities. Transient expression of GFP–HsvG or GFP–HsvB fusions in gypsophila, beet or melon leaves showed that HsvG and HsvB were localized to the nuclei of host and non‐host plants. A yeast one‐hybrid assay revealed that a single repeat of HsvG or HsvB was sufficient to activate transcription. By employing random binding‐site selection and gel‐shift assay HsvG was demonstrated to be a double‐stranded DNA‐binding protein with an ACACC/aAA consensus binding site. These results suggest that HsvG and HsvB are host‐specificity determinants and bear the potential to affect the host transcriptional machinery.
A glutamic acid 3‐methyltransferase encoded by an accessory gene locus important for daptomycin biosynthesis in Streptomyces roseosporus
Authors: Nguyen Kien T. , Kau David , Gu Jian‐Qiao , Brian Paul , Wrigley Stephen K. , Baltz Richard H. , Miao Vivian
Published: July 2006

In many peptide antibiotics, modified amino acids are important for biological activity. The amino acid 3‐methyl‐glutamic acid (3mGlu) has been found only in three cyclic lipopeptide antibiotics: daptomycin and the A21978C family produced by Streptomyces roseosporus, calcium‐dependent antibiotic produced by Streptomyces coelicolor and A54145 produced by Streptomyces fradiae. We studied the non‐ribosomal peptide synthetase genes involved in A21978C biosynthesis and the downstream genes, dptG, dptH, dptI and dptJ predicted to encode a conserved protein of unknown function, a thioesterase, a methyltransferase (MTase) and a tryptophan 2,3‐dioxygenase respectively. Deletion of dptGHIJ reduced overall lipopeptide yield and led to production of a series of novel A21978C analogues containing Glu12 instead of 3mGlu12. Complementation by only dptI, or its S. coelicolor homologue, glmT, restored the biosynthesis of the 3mGlu‐containing compounds in the mutant. Compared with A21978C, the Glu12‐containing derivatives were less active against Staphylococcus aureus. Further genetic analyses showed that members of the dptGHIJ locus cooperatively contributed to optimal A21978C production; deletion of dptH, dptI or dptJ genes reduced the yield significantly, while expression of dptIJ or dptGHIJ from the strong ermEp* promoter substantially increased lipopeptide production. The results indicate that these genes play important roles in the biosynthesis of daptomycin, and that dptI encodes a Glu MTase.
Fluctuating asymmetry and developmental instability in evolutionary biology: past, present and future
Authors: Dongen S. V.
Published: July 2006

The role of developmental instability (DI), as measured by fluctuating asymmetry (FA), in evolutionary biology has been the focus of a wealth of research for more than half a century. In spite of this long period and many published papers, our current state of knowledge reviewed here only allows us to conclude that patterns are heterogeneous and that very little is known about the underlying causes of this heterogeneity. In addition, the statistical properties of FA as a measure of DI are only poorly grasped because of a general lack of understanding of the underlying mechanisms that drive DI. If we want to avoid that this area of research becomes abandoned, more efforts should be made to understand the observed heterogeneity, and attempts should be made to develop a unifying statistical protocol. More specifically, and perhaps most importantly, it is argued here that more attention should be paid to the usefulness of FA as a measure of DI since many factors might blur this relationship. Furthermore, the genetic architecture, associations with fitness and the importance of compensatory growth should be investigated under a variety of stress situations. In addition, more focus should be directed to the underlying mechanisms of DI as well as how these processes map to the observable phenotype. These insights could yield more efficient statistical models and a unified approach to the analysis of patterns in FA and DI. The study of both DI and canalization is indispensable to obtain better insights in their possible common origin, especially because both have been suggested to play a role in both micro- and macro-evolutionary processes.
Prolonged storage of red blood cells affects aminophospholipid translocase activity
Authors: Verhoeven A. J. , Hilarius P. M. , Dekkers D. W. C. , Lagerberg J. W. M. , De Korte D.
Published: July 2006

Background and Objectives  Loss of phospholipid asymmetry in the membrane of red blood cells (RBC) results in exposure of phosphatidylserine (PS) and to subsequent removal from the circulation. In this study, we investigated the effect of long‐term storage of RBCs on two activities affecting phospholipid asymmetry: the ATP‐dependent aminophospholipid translocase (or flippase, transporting PS from the outer to the inner leaflet) and phospholipid scrambling (which will move PS from the inner to the outer leaflet).

Materials and Methods  Standard leukodepleted RBC concentrates were stored in saline‐adenine‐glucose‐mannitol (SAGM) at 4 °C for up to 7 weeks. PS exposure was determined by measurement of AnnexinV‐FITC binding to the cells, flippase activity by measurement of the inward translocation of NBD‐labelled PS. Scrambling activity was determined by following the inward translocation of fluorescent NBD‐phosphatidylcholine. In parallel, intracellular ATP levels were determined.

Results  PS exposure amounted to only 1·5 ± 0·3% positive cells (n = 8) after 5 weeks of storage, which slightly increased to 3·5 ± 0·7% (n = 8) after 7 weeks of storage. Flippase activity started to decrease after 21 days of storage and reached 81 ± 5% of the control value after 5 weeks of storage (n = 6) and 59 ± 6% (n = 6) after 7 weeks. Also in RBC obtained by apheresis, flippase activity decreased upon storage. Scrambling activity remained virtually absent during storage, explaining the low PS exposure despite the decrease in flippase activity. Rejuvenation of RBC after 7 weeks to increase ATP levels only partially restored flippase activity, but in combination with a correction of the intracellular pH to that of fresh cells, almost complete restoration was achieved. The decrease in flippase activity after prolonged storage did make the RBCs more prone to PS exposure after activation of phospholipid scrambling.

Conclusion  This study shows that, although PS exposure remains low, prolonged storage does compromise the RBC membrane by affecting flippase activity. When the metabolic changes induced by storage are corrected, flippase activity can be restored.
Incidence of Kawasaki disease in Japan: the nationwide surveys of 1999–2002
Authors: YANAGAWA HIROSHI , NAKAMURA YOSIKAZU , YASHIRO MAYUMI , UEHARA RITEI , OKI IZUMI , KAYABA KAZUNORI
Published: July 2006

Objective: The purpose of the present study was to describe the results of nationwide epidemiologic surveys of Kawasaki disease for the 4 year period 1999–2002.

Methods: The design is a retrospective incidence survey. The patients reported in these two surveys are all new patients who were reported during the two study periods (1999–2000 and 2001–2002), although the data were collected retrospectively. A questionnaire was sent to all pediatric departments of hospitals with 100 beds or more throughout Japan, requesting data on patients with Kawasaki disease, such as sex, age, date of first hospital visit, recurrence, and cardiac lesions.

Results: The total number of patients reported in the 4 year period 1999–2002 was 32 266 (18 604 male, 13 662 female), with an average annual incidence of 137.7 per 100 000 children younger than 5 years old. The male/female ratio was 1.30. The incidence peaked at 9–11 months of age, and the proportion of patients under 1 year of age was 26%. The monthly distribution had a high peak in January and a gradual increase in summer. Geographically, the high‐incidence areas were limited to certain prefectures and moved from year to year. The cardiac lesions at acute stage and cardiac sequelae occurred more in children under 1 year and older than 4 years. Among the principal symptoms, fever persisting ≥5 days occurred most commonly, followed by conjunctival congestion, changes in lips and oral cavity, polymorphous exanthema, and changes of extremities. Cervical lymphadenopathy occurred less.

Conclusion: More than 32 000 patients with Kawasaki disease during the 4 year period 1999–2002 were reported to the nationwide incidence surveys. The number of patients is steadily increasing despite the decrease of children. The seasonal variation, geographical distribution, and age‐specific distribution support the infection theory for the etiology of Kawasaki disease.
Results of clinical surveillance during the Japanese first palivizumab season in 2002–2003
Authors: KUSUDA SATOSHI , KOIZUMI TAKENOBU , SAKAI TAKEO , FUJIMURA MASANORI , NISHIDA HIROSHI , TOGARI HAJIME
Published: July 2006

Background: In Japan, palivizumab was approved in 2002 for prophylaxis of severe respiratory syncytial virus disease in high‐risk infants. In order to evaluate the efficacy and safety of this drug, a questionnaire survey was conducted.

Methods: A questionnaire was sent to member institutions of the Japan Neonatologist Association. The subjects were premature infants who were considered possible candidates for treatment with palivizumab.

Results: A total of 6302 case reports, including those of 2806 infants receiving palivizumab (group P) and 3496 infants not receiving palivizumab (group NP), respectively, were retrieved. Background characteristics revealed significant lower gestational age (GA) and birthweight for group P (P < 0.0001). Sex ratio did not differ significantly, while use of oxygen and mechanical ventilation in the neonatal intensive care unit, and presence of chronic lung disease were significantly higher for infants in group P (P < 0.0001). When comparison of hospitalization rate for respiratory symptoms was performed with stratification by eligibility criteria, in the group of infants born at 29–35 weeks GA the hospitalization rate was 4.0% and 5.7% in groups P and NP, respectively (P < 0.05). Multivariate analysis also showed that prophylaxis with palivizumab was the only variable that significantly decreased rate of hospitalization (odds ratio 0.630, P= 0.0053). The incidence of adverse events associated with the administration of palivizumab was low.

Conclusion: In this non‐randomized questionnaire survey, multivariate analysis showed that palivizumab significantly decreased the rate of hospitalization due to respiratory symptoms for infants born prematurely at 29–35 weeks GA. These data confirmed the efficacy and safety of palivizumab.
Topical treatment of molluscum contagiosum with imiquimod 5% cream in Turkish children
Authors: ARICAN OZER
Published: July 2006

Background: Molluscum contagiosum (MC) is caused by a poxvirus which produces cutaneous lesions appearing as small, firm, umblicated papules. Lesions of MC are most commonly seen in young children. Transmission is through viral particules, which remain on surfaces, autoinoculation, or from contact with open lesions. There are many options for treatment of MC and these may be broadly subdivided into destructive, immunological and antiviral therapies. An alternative treatment would be desirable in pediatric patients. Imiquimod (IQ) is a member of immune response modifiers.

Methods: Here, the results of 12 Turkish pediatric patients with MC who used IQ 5% cream (aged between 3–13 years; six boys, six girls) are given. The cream was applied by the mothers in the evening, three times per week every other day up to 16 weeks.

Results: One of the patients gave up the treatment because of Influenza‐like symptoms, and two of them because of the progress in the lesions continued. In seven of the remaining nine patients, total recovery was achieved. Local side‐effects in patients were well tolerated.

Conclusion: When all the patients affected with MC who exclusively used IQ 5% cream as mentioned in the literature were studied, 35 of 83 patients (42.2%) had complete clearance. These have differences in the form and duration of application. IQ 5% cream can be preferred in the treatment of children with MC because of its applicability at home, easy application and good tolerability. However, different application methods and suitable treatment methods should be determined.
Peer Rejection, Aggressive or Withdrawn Behavior, and Psychological Maladjustment from Ages 5 to 12: An Examination of Four Predictive Models
Authors: Ladd Gary W.
Published: July 2006

Findings yielded a comprehensive portrait of the predictive relations among children's aggressive or withdrawn behaviors, peer rejection, and psychological maladjustment across the 5–12 age period. Examination of peer rejection in different variable contexts and across repeated intervals throughout childhood revealed differences in the timing, strength, and consistency of this risk factor as a distinct (additive) predictor of externalizing versus internalizing problems. In conjunction with aggressive behavior, peer rejection proved to be a stronger additive predictor of externalizing problems during early rather than later childhood. Relative to withdrawn behavior, rejection's efficacy as a distinct predictor of internalizing problems was significant early in childhood and increased progressively thereafter. These additive path models fit the data better than did disorder‐driven or transactional models.
Maternal Chronological Age, Prenatal and Perinatal History, Social Support, and Parenting of Infants
Authors: Bornstein Marc H. , Putnick Diane L. , Suwalsky Joan T. D. , Gini Motti
Published: July 2006

The role of maternal chronological age in prenatal and perinatal history, social support, and parenting practices of new mothers (N=335) was examined. Primiparas of 5‐month‐old infants ranged in age from 13 to 42 years. Age effects were zero, linear, and nonlinear. Nonlinear age effects were significantly associated up to a certain age with little or no association afterward; by spline regression, estimated points at which the slope of the regression line changed were 25 years for prenatal and perinatal history, 31 years for social supports, and 27 years for parenting practices. Given the expanding age range of first‐time parents, these findings underscore the importance of incorporating maternal age as a factor in studies of parenting and child development.
Behavioral Control and Resiliency in the Onset of Alcohol and Illicit Drug Use: A Prospective Study From Preschool to Adolescence
Authors: Wong Maria M. , Nigg Joel T. , Zucker Robert A. , Puttler Leon I. , Fitzgerald Hiram E. , Jester Jennifer M. , Glass Jennifer M. , Adams Kenneth
Published: July 2006

The developmental trajectories of behavioral control and resiliency from early childhood to adolescence and their effects on early onset of substance use were examined. Behavioral control is the tendency to express or contain one's impulses and behaviors. Resiliency is the ability to adapt flexibly one's characteristic level of control in response to the environment. Study participants were 514 children of alcoholics and matched controls from a longitudinal community sample (Time 1 age in years: M=4.32, SD=0.89). Children with slower rates of increase in behavioral control were more likely to use alcohol and other drugs in adolescence. Children with higher initial levels of resiliency were less likely to begin using alcohol.
When Victims Don't Cry: Children's Understandings of Victimization, Compliance, and Subversion
Authors: Shaw Leigh A , Wainryb Cecilia
Published: July 2006

How do children understand situations in which the targets of moral transgressions do not complain about the way they are treated? One –hundred and twenty participants aged 5, 7, 10, 13, and 16 years were interviewed about hypothetical situations in which one child (“transgressor”) made an apparently unfair demand of another child (“victim”), who then responded by either resisting, complying, or subverting. In general, 5‐year‐olds judged compliance positively and resistance negatively and 7‐ to 16‐year‐olds judged resistance positively and compliance negatively; all but 16‐year‐olds judged subversion negatively. Most participants judged the transgressor's actions negatively, regardless of how the victim had responded. The findings are discussed in terms of their implications for children's developing understandings of victimization.
Guaranteed Manufactured without Child Labor: The Economics of Consumer Boycotts, Social Labeling and Trade Sanctions
Authors: Basu Arnab K. , Chau Nancy H. , Grote Ulrike
Published: July 2006

Does labeling products “Child‐Labor Free” provide a market‐based solution to the pervasive employment of child labor? This paper explores the promise of social labeling in the context of its four oft‐noted objectives: child labor employment, consumer information, welfare, and trade linkages, when competition between the North and South is based both on comparative cost advantage, and the use of child labor as a hidden product attribute. We show that (i) social labeling benefits consumers and Southern producers, whereas children and Northern producers are worse off; (ii) trade sanctions on unlabeled products deteriorates Southern terms of trade, but leaves the incidence of child labor strictly unaffected; and (iii) a threat to sanction imports of unlabeled Southern products discourages the South from maintaining a credible social labeling program. We also explore the question of whether social labeling should be viewed as a transitory or a permanent institution in developing economies.
Are Donor Countries Giving More or Less Aid?
Authors: Gupta Sanjeev , Pattillo Catherine , Wagh Smita
Published: July 2006

The volume of foreign aid has increased during the last four decades, albeit with interruptions in certain years. Over time, the major recipients have changed: while the share of aid to Asia has diminished since the 1980s, that destined for sub‐Saharan Africa has grown. There is some evidence that, since the late 1990s, debt relief has assumed a larger share of the increased aid flows to sub‐Saharan Africa. The share of technical cooperation—a component of aid that is viewed as being driven by donors—has risen. More recently, there has been an increased emphasis on providing budget support to recipient governments, especially in the form of debt relief. Donor harmonization, national ownership of development plans, and sound policies on the part of the recipients are crucial for the aid to be effective in reducing poverty.