bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid GAL Gene Switch of Saccharomyces cerevisiae Depends on Nuclear Gal3, Not Nucleocytoplasmic Trafficking of Gal3 and Gal80
Authors: Egriboz Onur , Jiang Fenglei , Hopper James E 
Published: September 2011

Abstract
The yeast transcriptional activator Gal4 localizes to UASGAL sites even in the absence of galactose but cannot activate transcription due to an association with the Gal80 protein. By 4 min after galactose addition, Gal4-activated gene transcription ensues. It is well established that this rapid induction arises through a galactose-triggered association between the Gal80 and Gal3 proteins that decreases the association of Gal80 and Gal4. How this happens mechanistically remains unclear. Strikingly different hypotheses prevail concerning the possible roles of nucleocytoplasmic distribution and trafficking of Gal3 and Gal80 and where in the cell the initial Gal3–Gal80 association occurs. Here we tested two conflicting hypotheses by evaluating the subcellular distribution and dynamics of Gal3 and Gal80 with reference to induction kinetics. We determined that the rates of nucleocytoplasmic trafficking for both Gal80 and Gal3 are slow relative to the rate of induction. We find that depletion of the nuclear pool of Gal3 slows the induction kinetics. Thus, nuclear Gal3 is critical for rapid induction. Fluorescence-recovery-after-photobleaching experiments provided data suggesting that the Gal80–Gal4 complex exhibits kinetic stability in the absence of galactose. Finally, we detect Gal3 at the UASGAL only if Gal80 is covalently linked to the DNA-binding domain. Taken altogether, these new findings lead us to propose that a transient interaction of Gal3 with Gal4-associated Gal80 could explain the rapid response of this system. This notion could also explain earlier observations.
MicroRNA Sequence Variation Potentially Contributes to Within-Species Functional Divergence in the NematodeCaenorhabditis briggsae
Authors: Jovelin Richard , Cutter Asher D 
Published: September 2011

AbstractMounting evidence points to differences in gene regulation as a major source of phenotypic variation. MicroRNA-mediated post-transcriptional regulation has emerged recently as a key factor controlling gene activity during development. MicroRNA genes are abundant in genomes, acting as managers of gene expression by directing translational repression. Thus, understanding the role of microRNA sequence variation within populations is essential for fully dissecting the origin and maintenance of phenotypic diversity in nature. In this study, we investigate allelic variation at microRNA loci in the nematode Caenorhabditis briggsae, a close relative of C. elegans. Phylogeographic structure in C. briggsae partitions most strains from around the globe into a “temperate” or a “tropical” clade, with a few strains having divergent, geographically restricted genotypes. Remarkably, strains that follow this latitudinal dichotomy also differ in temperature-associated fitness. With this phylogeographic pattern in mind, we examined polymorphisms in 18 miRNAs in a global sample of C. briggsae isolates and tested whether newly isolated strains conform to this phylogeography. Surprisingly, nucleotide diversity is relatively high in this class of gene that generally experiences strong purifying selection. In particular, we find that miRNAs in C. briggsae are substantially more polymorphic than in Arabidopsis thaliana, despite similar background levels of neutral site diversity between the two species. We find that some mutations suggest functional divergence on the basis of requirements for target site recognition and computational prediction of the effects of the polymorphisms on RNA folding. These findings demonstrate the potential for miRNA polymorphisms to contribute to phenotypic variation within a species. Sequences were deposited in GenBank under accession nos. JN251323–JN251744.
Fitness Landscapes: An Alternative Theory for the Dominance of Mutation
Authors: Manna Federico , Martin Guillaume , Lenormand Thomas 
Published: September 2011

Abstract
Deleterious mutations tend to be recessive. Several theories, notably those of Fisher (based on selection) and Wright (based on metabolism), have been put forward to explain this pattern. Despite a long-lasting debate, the matter remains unresolved. This debate has focused on the average dominance of mutations. However, we also know very little about the distribution of dominance coefficients among mutations, and about its variation across environments. In this article we present a new approach to predicting this distribution. Our approach is based on a phenotypic fitness landscape model. First, we show that under a very broad range of conditions (and environments), the average dominance of mutation of small effects should be approximately one-quarter as long as adaptation of organisms to their environment can be well described by stabilizing selection on an arbitrary set of phenotypic traits. Second, the theory allows predicting the whole distribution of dominance coefficients among mutants. Because it provides quantitative rather than qualitative predictions, this theory can be directly compared to data. We found that its prediction on mean dominance (average dominance close to 0.25) agreed well with the data, based on a meta-analysis of dominance data for mildly deleterious mutations. However, a simple landscape model does not account for the dominance of mutations of large effects and we provide possible extension of the theory for this class of mutations. Because dominance is a central parameter for evolutionary theory, and because these predictions are quantitative, they set the stage for a wide range of applications and further empirical tests.
Statistical Uncertainty of Mortality Rates and Rankings for Children's Hospitals
Authors: Feudtner Chris , Berry Jay G. , Parry Gareth , Hain Paul , Morse Rustin B. , Slonim Anthony D. , Shah Samir S. , Hall Matt 
Published: September 2011

OBJECTIVES:
Hospitals are being required to report publically their adjusted mortality rates, which are then being used to rank hospitals. Our objectives were to assess the statistical reliability of the determination of a hospital's adjusted mortality rate, of comparisons of that rate with the rates of other hospitals, and of the use of those rates to rank the hospitals.

METHODS:
A cross-sectional study of 473 383 patients discharged from 42 US children's hospitals in 2008 was performed. Hospital-specific observed/expected (O/E) mortality rate ratios and corresponding hospital rankings, with 95% confidence intervals (CIs), were examined.

RESULTS:
Hospitals' O/E mortality rate ratios exhibited wide 95% CIs, and no hospital was clearly distinguishable from the other hospitals' aggregated mean mortality performance. Only 2 hospitals' mortality performance fell outside the comparator hospitals' 95% CI. Those hospitals' 95% CIs overlapped with the overall comparator set's 95% CI, which suggests that there were no statistically significant hospital outliers. Fourteen (33.3%) of the 42 hospitals had O/E ratios that were not statistically different from being in the 95% CI of the top 10% of hospitals. Hospital-specific mortality rate rankings displayed even broader 95% CIs; the typical hospital had a 95% CI range that spanned 22 rank-order positions.

CONCLUSION:
Children's hospital-specific measures of adjusted mortality rate ratios and rankings have substantial amounts of statistical imprecision, which limits the usefulness of such measures for comparisons of quality of care.
Recurrence and Outcomes of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Children
Authors: Finkelstein Yaron , Soon Gordon S. , Acuna Patrick , George Mathew , Pope Elena , Ito Shinya , Shear Neil H. , Koren Gideon , Shannon Michael W. , Garcia-Bournissen Facundo 
Published: September 2011

OBJECTIVES:
To report clinical course, etiology, management, and long-term outcomes of children suffering from Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN).

METHODS:
We conducted a study of all pediatric patients with SJS or TEN admitted between 2000 and 2007 to the Hospital for Sick Children and Children's Hospital Boston, and particular attention was paid to clinical manifestations, etiology, mortality, and long-term outcomes.

RESULTS:
We identified 55 cases of SJS (n = 47), TEN (n = 5), or SJS/TEN overlap syndrome (n = 3). Drugs were identified as the most likely etiologic agent in 29 children (53%); antiepileptic drugs were the most common agents (n = 16), followed by sulfonamide antibiotics (n = 7) and chemotherapy drugs (n = 2). Acute Mycoplasma pneumoniae infection was confirmed in 12 children (22%), and herpes simplex virus was confirmed in 5 children (9%). Treatment regimens differed significantly between participating sites and included systemic antimicrobial agents (67%), systemic corticosteroids (40%), and antiviral drugs (31%). Intravenous immunoglobulin was administered to 21 children (38%), of whom 8 received concomitant systemic corticosteroids. Ten children (18%) had recurrence of SJS up to 7 years after the index episode, and 3 experienced multiple recurrences. Twenty-six children (47%) suffered long-term sequelae that mostly involved the skin and eyes.

CONCLUSIONS:
Mortality rate in children was lower than that reported in adults, but half of affected children suffered long-term complications. The recurrence rate of SJS was high (1 in 5), which suggests vulnerability and potential genetic predisposition. In the absence of standardized management guidelines for these conditions, treatment regimens differed significantly between participating institutions.
Age-Specific Differences in Outcomes After Out-of-Hospital Cardiac Arrests
Authors: Nitta Masahiko , Iwami Taku , Kitamura Tetsuhisa , Nadkarni Vinay M. , Berg Robert A. , Shimizu Naoki , Ohta Kunio , Nishiuchi Tatsuya , Hayashi Yasuyuki , Hiraide Atsushi , Tamai Hiroshi , Kobayashi Masanao , Morita Hiroshi ,   for the Utstein Osaka Project
Published: September 2011

OBJECTIVE:We assessed out-of-hospital cardiac arrests (OHCAs) for various pediatric age groups.METHODS:This prospective, population-based, observational study included all emergency medical service-treated OHCAs in Osaka, Japan, between 1999 and 2006 (excluding 2004). Patients were grouped as adults (&gt;17 years), infants (&lt;1 year), younger children (1–4 years), older children (5–12 years), and adolescents (13–17 years). The primary outcome measure was 1-month survival with favorable neurologic outcome.RESULTS:Of 950 pediatric OHCAs, resuscitations were attempted for 875 patients (92%; 347 infants, 203 younger children, 135 older children, and 190 adolescents). The overall incidence of nontraumatic pediatric OHCAs was 7.3 cases per 100 000 person-years, compared with 64.7 cases per 100 000 person-years for adults and 65.5 cases per 100 000 person-years for infants. Most infant OHCAs occurred in homes (93%) and were not witnessed (90%). Adolescent OHCAs often occurred outside the home (45%), were witnessed by bystanders (37%), and had shockable rhythms (18%). One-month survival was more common after nontraumatic pediatric OHCAs than adult OHCAs (8% [56 of 740 patients] vs 5% [1677 of 33 091 patients]; adjusted odds ratio: 2.26 [95% confidence interval: 1.63–3.13]). One-month survival with favorable neurologic outcome was more common among children than adults (3% [21 of 740 patients] vs 2% [648 of 33 091 patients]; adjusted odds ratio: 2.46 [95% confidence interval: 1.45–4.18]). Rates of 1-month survival with favorable neurologic outcome were 1% for infants, 2% for younger children, 2% for older children, and 11% for adolescents.CONCLUSION:Survival and favorable neurologic outcome at 1 month were more common after pediatric OHCAs than adult OHCAs.
Risk Factors for Childhood Mental Health Symptoms: National Longitudinal Study of Australian Children
Authors: Bayer Jordana K. , Ukoumunne Obioha C. , Lucas Nina , Wake Melissa , Scalzo Katherine , Nicholson Jan M. 
Published: September 2011

OBJECTIVE:To determine predictors of child externalizing (behavioral) and internalizing (emotional) symptoms in a national population sample.METHODS:Data were collected in 3 biennial waves (2004, 2006, and 2008) from 2 cohorts in the Longitudinal Study of Australian Children, initially including 5107 children 0 to 1 year of age and 4983 children 4 to 5 years of age. The primary outcomes were child externalizing and internalizing symptoms. Relationships between potential risk factors and child mental health outcomes were described by using linear regression.RESULTS:In unadjusted analyses, children's mental health symptoms were predicted by a large number of risk factors. In multivariate models, early childhood factors (birth through 5 years) explained 30% and 18% of variations in externalizing and internalizing symptoms, respectively, at 4 to 5 years of age. Middle childhood (5–9 years of age) factors explained 20% and 23% of variations in externalizing and internalizing symptoms, respectively, at 8 to 9 years of age. Harsh discipline was a strong consistent predictor of externalizing symptoms in both age groups, whereas poorer child physical health, maternal emotional distress, harsh discipline, and overinvolved/protective parenting (younger cohort only) predicted internalizing symptoms consistently.CONCLUSIONS:National data on predictors of child mental health symptoms highlighted a small number of significant risk factors, situated in the family context and present from a very young age. This knowledge is informing population-level, randomized, prevention trials of family support programs.
Race, Ancestry, and Development of Food-Allergen Sensitization in Early Childhood
Authors: Kumar Rajesh , Tsai Hui-Ju , Hong Xiumei , Liu Xin , Wang Guoying , Pearson Colleen , Ortiz Katherin , Fu Melanie , Pongracic Jacqueline A. , Bauchner Howard , Wang Xiaobin 
Published: September 2011

OBJECTIVE:
We examined whether the risk of food-allergen sensitization varied according to self-identified race or genetic ancestry.

METHODS:
We studied 1104 children (mean age: 2.7 years) from an urban multiethnic birth cohort. Food sensitization was defined as specific immunoglobulin E (sIgE) levels of ≥0.35 kilo–units of allergen (kUA)/L for any of 8 common food allergens. Multivariate logistic regression analyses were used to evaluate the associations of self-identified race and genetic ancestry with food sensitization. Analyses also examined associations with numbers of food sensitizations (0, 1 or 2, and ≥3 foods) and with logarithmically transformed allergen sIgE levels.

RESULTS:
In this predominantly minority cohort (60.9% black and 22.5% Hispanic), 35.5% of subjects exhibited food sensitizations. In multivariate models, both self-reported black race (odds ratio [OR]: 2.34 [95% confidence interval [CI]: 1.24–4.44]) and African ancestry (in 10% increments; OR: 1.07 [95% CI: 1.02–1.14]) were associated with food sensitization. Self-reported black race (OR: 3.76 [95% CI: 1.09–12.97]) and African ancestry (OR: 1.19 [95% CI: 1.07–1.32]) were associated with a high number (≥3) of food sensitizations. African ancestry was associated with increased odds of peanut sIgE levels of ≥5 kUA/L (OR: 1.25 [95% CI: 1.01–1.52]). Similar ancestry associations were seen for egg sIgE levels of ≥2 kUA/L (OR: 1.13 [95% CI: 1.01–1.27]) and milk sIgE levels of ≥5 kUA/L (OR: 1.24 [95% CI: 0.94–1.63]), although findings were not significant for milk.

CONCLUSIONS:
Black children were more likely to be sensitized to food allergens and were sensitized to more foods. African ancestry was associated with peanut sensitization.
School Absenteeism Among Children Living With Smokers
Authors: Levy Douglas E. , Winickoff Jonathan P. , Rigotti Nancy A. 
Published: September 2011

OBJECTIVE:Involuntary tobacco smoke exposure causes substantial morbidity in children. We hypothesized that children exposed to tobacco smoke in the home would have increased school absenteeism with associated costs due to lost caregiver wages/time.METHODS:We analyzed data on health and absenteeism among schoolchildren aged 6 to 11 years identified in the 2005 National Health Interview Survey (NHIS). We used multivariate models to assess the relationships between adult-reported household smoking and child health and school absenteeism. Analyses were adjusted for children's and parents' demographic and socioeconomic characteristics. The value of lost caregiver time was estimated by using self-reported employment and earnings data in the NHIS and publicly available time-use data.RESULTS:Children living with 1 or ≥2 adults who smoked in the home had 1.06 (95% confidence interval [CI]: 0.54–1.55) and 1.54 (95% CI: 0.95–2.12) more days absent from school per year, respectively, than children living with 0 smokers in the home. Living with ≥2 adults who smoked in the home was associated with increased reports of having ≥3 ear infections in the previous 12 months (adjusted odds ratio [aOR]: 2.65 [95% CI: 1.36–5.16]) and having a chest cold in the 2 weeks before interview (aOR: 1.77 [95% CI: 1.03–3.03]) but not with having vomiting/diarrhea in the previous 2 weeks (aOR: 0.93 [95% CI: 0.45–1.89]). Caregivers' time tending children absent from school was valued at $227 million per year.CONCLUSIONS:Tobacco smoke exposure has significant consequences for children and families above and beyond child morbidity, including academic disadvantage and financial burden.
Evaluating Restoration Methods across a Range of Plant Communities Dominated by Invasive Annual Grasses to Native Perennial Grasses
Authors: Nyamai Priscilla A. , Prather Timothy S. , Wallace John M. 
Published: September 2011

AbstractPrairies are imperiled habitats, with remnants being generally small and often existing in isolation. Invasive plants have the potential to invade not just the edge of small remnants but also the interior because smaller remnants experience greater edge effects than do large, contiguous prairies. Additionally, invasive plants limit recruitment of native plants, which can arrest secondary succession. We proposed to assess techniques for restoration that included removing annual grasses and supplementing native species recruitment with seeding of native grass and forb species. We also assessed the effect of specific factors affecting recruitment: soil moisture and seed predation. Treatments included broadcast, spot, or no application of the herbicides imazapic and glyphosate and with or without seeding plus mulch. With treatments nested within each of three plant communities, ranging from annual- to perennial-dominated communities, in four blocks per community, plant characteristics (percentage of cover and plant density), soil moisture availability, and seed-predation losses were measured along a plant community gradient within one season at two locations. A combination of broadcast herbicide application and seeding with mulching was found to be more effective in reducing annual grasses and enhancing the establishment of native grass species in predominately annual and mixed communities (annuals and perennials). Spot herbicide application was effective in predominately perennial communities, whereas only seeding native species did not improve recruitment. Although seed predation reduced seedling recruitment, mulch provided seed protection and enhanced soil moisture retention. Plant community response to imposed treatments differed among communities, suggesting that a decision support tool would facilitate management decisions tailored for each plant community. The decision tool would be useful to ensure that appropriate treatments are applied and that specific factors affecting recruitment, such as seed predation and soil moisture, are addressed.
Using Rangeland Health Assessment to Inform Successional Management
Authors: Sheley Roger L. , James Jeremy J. , Vasquez Edward A. , Svejcar Tony J. 
Published: September 2011

AbstractRangeland health assessment provides qualitative information on ecosystem attributes. Successional management is a conceptual framework that allows managers to link information gathered in rangeland health assessment to ecological processes that need to be repaired to allow vegetation to change in a favorable direction. The objective of this paper is to detail how these two endeavors can be integrated to form a holistic vegetation management framework. The Rangeland Health Assessment procedures described by Pyke et al. (2002) and Pellant et al. (2005) currently are being adopted by land managers across the western United States. Seventeen standard indicators were selected to represent various ecological aspects of ecosystem health. Each of the indicators is rated from extreme to no (slight) departure from the Ecological Site Description and/or the Reference Area(s). Successional management identifies three general drivers of plant community change: site availability, species availability, and species performance, as well as specific ecological processes influencing these drivers. In this paper, we propose and provide examples of a method to link the information collected in rangeland health assessment to the successional management framework. Thus, this method not only allows managers to quantify a point-in-time indication of rangeland health but also allows managers to use this information to decide how various management options might influence vegetation trajectories. We argue that integrating the Rangeland Health Assessment with Successional Management enhances the usefulness of both systems and provides synergistic value to the decision-making process.
The analysis of historical seismograms: an important tool for seismic hazard assessment. Case histories from French and Italian earthquakes
Authors: Pino Nicola Alessandro 
Published: September 2011

AbstractSeismic hazard assessment relies on the knowledge of the source characteristics of past earthquakes. Unfortunately, seismic waveform analysis, representing the most powerful tool for the investigation of earthquake source parameters, is only possible for events occurred in the last 100–120 years, i.e., since seismographs with known response function were developed. Nevertheless, during this time significant earthquakes have been recorded by such instruments and today, also thanks to technological progress, these data can be recovered and analysed by means of modern techniques.In this paper, aiming at giving a general sketch of possible analyses and attainable results in historical seismogram studies, I briefly describe the major difficulties in processing the original waveforms and present a review of the results that I obtained from previous seismogram analysis of selected significant historical earthquakes occurred during the first decades of the XXth century, including (A) the December 28, 1908, Messina straits (southern Italy), (B) the June 11, 1909, Lambesc (southern France) – both of which are the strongest ever recorded instrumentally in their respective countries –and (C) the July 13, 1930, Irpinia (southern Italy) events. For these earthquakes, the major achievements are represented by the assessment of the seismic moment (A, B, C), the geometry and kinematics of faulting (B, C), the fault length and an approximate slip distribution (A, C). The source characteristics of the studied events have also been interpreted in the frame of the tectonic environment active in the respective region of interest. In spite of the difficulties inherent to the investigation of old seismic data, these results demonstrate the invaluable and irreplaceable role of historical seismogram analysis in defining the local seismogenic potential and, ultimately, for assessing the seismic hazard. The retrieved information is crucial in areas where important civil engineering works are planned, as in the case of the single-span bridge to be built across the Messina straits and the ITER nuclear fusion power plant to be built in Cadarache, close to the location of the Lambesc event, and in regions characterized by high seismic risk, such as southern Apennines.