bluuebunny/crossref_metadata_2025 huggingface dataset:
Guidelines for the effective use of chemical inhibitors of protein function to understand their roles in cell regulation
Authors: Cohen Philip
Published: December 2009

Cell-permeable chemical inhibitors have become invaluable reagents for the study of cellular regulation. In the present paper, using protein kinase inhibitors as the example, a set of criteria are described that should be met before any investigation using such compounds should be accepted for publication.
Continuous monitoring of ruminal pH using wireless telemetry
Authors: Phillips N. , Mottram T. , Poppi D. , Mayer D. , McGowan M. R.
Published: December 2009

This paper describes the performance of a prototype telemetric intraruminal bolus that measures and records pH continuously, can be delivered orally to the reticulum via bolling gun, has no external attachments and allows unrestricted activity of the animal. When interrogated by wireless the bolus transmits the recorded data to an operator standing beside the animal with a handheld receiving station. Boluses were placed in fistulated animals to enable direct comparison with samples obtained directly from the rumen and measured with a laboratory instrument. Overall, the mean (±s.d.) pH recorded on the manually collected samples (pH 6.64 ± 0.67) was generally less than that of the continuously measured telemetric system (pH 7.03 ± 0.54) with a correlation of r = 0.93 (P < 0.01). Data are presented to show typical diurnal and grain-enforced changes in pH recorded in a rumen over a 70-day period. The development of the Well Cow pH bolus device potentially enables researchers, dairy farmers and feedlot managers to monitor rumen function of any ruminant over prolonged periods without the need for invasive sampling. Enemark et al. (2003) considered that a 14–21-day observational period is required to properly monitor for conditions such as subacute ruminal acidosis. Whilst significant correlation (P < 0.01; r = 0.982) existed between the two readings for the first 40 days of continuous recording, the Well Cow pH bolus reading started to deviate significantly from the directly measured value thereafter. Regardless, a continuously measuring functional life of up to 40 days indicates that the current prototype has the capacity to accurately detect subacute ruminal acidosis.
Effects of ad libitum mineral consumption in Iberian red deer hinds and calves
Authors: Ceacero Francisco , Landete-Castillejos Tomás , García Andrés J. , Estévez José A. , Gaspar-López Enrique , Gallego Laureano
Published: December 2009

Minerals are essential nutrients for ungulates because they cannot be synthesised. Lactation is the most mineral-demanding stage for hinds, whereas for calves both the pre- and post-weaning growth periods are important for bone formation, among other processes. Because both physiological effort and hot Mediterranean climate may increase mineral needs even in a situation under an ad libitum high plane of nutrition, we examined the effects of free-choice, single-mineral consumption in red deer hinds and their calves during lactation, and in the calves, from 18 to 56 weeks after lactation. Group M had permanent access to minerals, the control group had no access, whereas the LM and PLM groups of calves had access to minerals only during lactation or after lactation, respectively. Hinds with or without mineral supplements during lactation did not show differences in weight or body condition, neither did female calves of any group during or after lactation. However, after controlling the effect of year, LM male calves achieved greater weight gains during the post-lactation experiment, whereas the PLM and M groups showed negative results in weight at the end of the post-lactation experiment and age of antler growth initiation, respectively. The LM group also achieved higher scores in all the studied first antler variables (length, weight, burr perimeter, and perimeter in the middle of the antler) after controlling the effects of weight and year. The results thus suggest that, under ad libitum access to high-quality food, mineral supplementation is only positive during lactation. However, it cannot be ruled out that minerals may be beneficial in other stages in free-ranging deer.
Feed intake, digestibility, and carcass characteristics of lambs fed a diet supplemented with soluble fibre
Authors: Bodas R. , López S. , Rodríguez A. B. , Andrés S. , Mantecón A. R. , Giráldez F. J.
Published: December 2009

Thirty-six Merino lambs (8–9 weeks of age and 15.3 ± 0.13 kg of initial liveweight) were used to evaluate the effects of the inclusion of 120 g sugar beet pulp (replacing barley) and the addition of 20 g sodium bicarbonate per kg concentrate on feed intake, digestibility, animal performance and carcass characteristics in fattening lambs. Animals were housed individually and fed barley straw and the corresponding experimental concentrate feed ad libitum [basal diet composed of (g/kg) barley (500), maize (230), soybean meal (190), molasses (50) and vitamin premix (30)]. Faeces were collected for 5 days to estimate digestibility. Lambs were slaughtered when they reached 25 kg liveweight. Carcasses were chilled at 4°C for 24 h, some carcass dimensions were calculated, the left carcass was jointed into commercial cuts and shoulder tissue composition determined. Sugar beet pulp decreased DM intake (P < 0.05) and average daily gain (P < 0.001), increasing feed : gain ratio (P < 0.001), whereas sodium bicarbonate increased neutral detergent fibre digestibility (P < 0.05) and average daily gain, reducing the feed : gain ratio (P < 0.05). Carcass characteristics were not affected (P > 0.05) by either sodium bicarbonate or sugar beet pulp. Replacing barley with 120 g sugar beet pulp/kg concentrate caused a decrease in DM intake and average daily gain, resulting in an increase in feed : gain ratio, with no detrimental effect on carcass characteristics. The addition of 20 g sodium bicarbonate/kg concentrate improved intake and animal performance without affecting carcass characteristics. Inclusion of sugar beet pulp as a replacement for barley in high-concentrate diets for fattening lambs did not produce performance responses similar to those observed by adding a buffering salt.
A financial analysis of lime application in a long-term agronomic experiment on the south-western slopes of New South Wales
Authors: Li Guangdi D. , Singh Rajinder P. , Brennan John P. , Helyar Keith R.
Published: December 2009

Management of Acid Soils Through Efficient Rotations (MASTER) is a long-term agronomic experiment commenced in 1992. There were 3 fundamental treatment contrasts in this experiment: (a) annual systems v. perennial systems; (b) limed v. unlimed treatments; and (c) permanent pastures v. pasture–crop rotations. The soil was acidic to depth with pH (in CaCl2) below 4.5 and exchangeable Al above 40% at 0.10–0.20 m when the experiment started. Lime was applied every 6 years to maintain soil pHCa at 5.5 in the 0–0.10 m soil depth. A financial analysis was undertaken to estimate potential benefits and costs involved in liming acid soils on the south-western slopes of New South Wales, based on data from the MASTER experiment. The most important finding from the current study is that liming pastures on soils that have a subsurface acidity problem is profitable over the long-term for productive livestock enterprises. The pay-back period for liming pastures, grazed by Merino wethers, was 14 years for both annual and perennial pastures. More profitable livestock enterprises, such as prime lambs or growing-out steers, were estimated to reduce the pay-back period. This gives farmers confidence to invest in a long-term liming program to manage highly acid soils in the traditional permanent pasture region of the high-rainfall zone (550–800 mm) of south-eastern Australia. Results from the current study also confirmed that the total financial return from liming is greater if the land is suitable for operation of a pasture–crop rotation system. The positive cash flows generated from cropping in a relatively short time can significantly shorten the pay-back period for the investment in lime. But cropping without liming on soils with subsurface acidity was worse than grazing animals. Crop choice is crucial for the perennial pasture–crop rotation. Inclusion of high-value cash crops, such as canola or a wheat variety with high protein, would lead to a rise in the aggregate benefits over time as the soil fertility improved and soil acidity was gradually ameliorated.
Fertiliser N and P application on two Vertosols in north-eastern Australia. 3. Grain N uptake and yield by crop/fallow combination, and cumulative grain N removal and fertiliser N recovery in grain
Authors: Lester David W. , Birch Colin J. , Dowling Chris W.
Published: December 2009

The grain N uptake response of an opportunity cropping regime comprising summer and winter cereal and legume crops to fertiliser nitrogen (N) and phosphorus (P) applications was studied in 2 long-term experiments with contrasting durations of cultivation. At the longer cultivation duration Colonsay site (>44 years at commencement), grain N uptake increased with fertiliser N application in 15 of 17 harvested crops from 1985 to 2003. Grain sorghum on short-fallow consistently responded to applied fertiliser N at higher rates (≥80 kg N/ha) than crops grown on long-fallow where either fertiliser at nil or 40 kg N/ha maximised grain N uptake. Winter cereal response to applied N was influenced by fallow length, generally smaller responses in long fallow years, although in-crop rainfall affected this. Short-fallow crops responded up to 40 or 80 kg applied N/ha, while seasonal growing-season rainfall affected the responses of the double-crop winter cereals the most. Responses to applied fertiliser N at the shorter duration cultivation Myling site (9 years at commencement) generally occurred only under high-intensity cropping periods, or in those crops sown following periods of slower potential N mineralisation. Phosphorus fertiliser application influenced grain N uptake at both locations in some years, with winter cereals, legumes, and sorghum sown following long-fallow generally significant.
Cumulative grain N uptakes in both experiments were independently influenced by fertiliser N and P treatments, P having an additive effect, increasing grain yield and grain N removed. Recovery efficiency of fertiliser N in grain, derived from cumulative N fertiliser application and grain N uptake, in general declined as amount of fertiliser N applied increased; however, as N supplies became less limiting to yield, P fertiliser generated higher fertiliser N recovery in grain. At Colonsay, RENG from cumulative uptake and removal was ≥0.48 with fertiliser P application for cumulative fertiliser N input ≤1340 kg N/ha (≈80 kg fertiliser N/ha.crop).
Resistance to clover scorch disease (Kabatiella caulivora) among accessions of purple clover (Trifolium purpureum) and its relationship to the eco-geography of collection sites
Authors: Nichols P. G. H. , Snowball R. , D'Antuono M. F. , Barbetti M. J.
Published: December 2009

Visual ratings of disease reaction to a mixture of races 1 and 2 of clover scorch (Kabatiella caulivora) were conducted on inoculated field plots of 206 accessions of Trifolium purpureum (191 var. purpureum and 15 var. pamphyllicum) collected from the Mediterranean basin and surrounding regions. Disease severity scores of the resistant check, cv. Denmark subterranean clover (T. subterraneum), were clearly differentiated from the susceptible check, cv. Paratta purple clover. Nearly 33% of the accessions were resistant to both races. Resistant plants tended to flower later and originate from higher latitudes, where K. caulivora is more widespread. The results of this investigation led to development of ELECTRA™, the first cultivar of purple clover with resistance to both races of K. caulivora.
Quantification of natural DOM from UV absorption at two wavelengths
Authors: Tipping Edward , Corbishley Heather T. , Koprivnjak Jean-Francois , Lapworth Daniel J. , Miller Matthew P. , Vincent Colin D. , Hamilton-Taylor John
Published: December 2009

Environmental context. Dissolved organic matter (DOM) is part of the global carbon cycle, ecologically and geochemically active, and costly to remove in water treatment. Spectroscopic monitoring at a single wavelength provides some indication of DOM concentration, but variations in optical properties mean that accurate determinations currently rely on slow and costly laboratory methods. We show that for water samples containing non-anthropogenic DOM, ultraviolet absorbance at two wavelengths can quantify DOM rapidly, cheaply and accurately, and also indicate its quality.
Abstract. The precise simulation of ultraviolet absorption by 23 contrasting surface-water DOM samples was achieved with a model based on two components, one absorbing light strongly (A) and the other weakly (B). The parameterised model can be used to predict [DOC] in water samples simply from absorbance values at two wavelengths, while information on DOM quality is provided by the calculated fractionation into A and B. The model was tested by predicting [DOC] for a separate dataset obtained by combining results for 12 samples each from surface waters in the UK, Canada and the USA, and from UK groundwaters. A close correlation (R2 = 0.997) was obtained, with only slight underestimation of the true [DOC]. The proportions of components A and B varied considerably among the sites, which explains why precise prediction of [DOC] from absorbance data at a single wavelength was not possible. When the model was applied to samples collected from river locations in a heterogeneous UK catchment with areas of industry and high human population, [DOC] was underestimated in many cases, which may indicate the presence of non-absorbing pollutant DOM.
NMR analysis of G-protein βγ subunit complexes reveals a dynamic Gα-Gβγ subunit interface and multiple protein recognition modes
Authors: Smrcka Alan V. , Kichik Nessim , Tarragó Teresa , Burroughs Michael , Park Min-Sun , Itoga Nathan K. , Stern Harry A. , Willardson Barry M. , Giralt Ernest
Published: December 2009

G-protein βγ (Gβγ) subunits interact with a wide range of molecular partners including: Gα subunits, effectors, peptides, and small molecule inhibitors. The molecular mechanisms underlying the ability to accommodate this wide range of structurally distinct binding partners are not well understood. To uncover the role of protein flexibility and alterations in protein conformation in molecular recognition by Gβγ, a method for site-specific15N-labeling of Gβ-Trp residue backbone and indole amines in insect cells was developed. Transverse Relaxation Optimized Spectroscopy-Heteronuclear Single-Quantum Coherence Nuclear Magnetic Resonance (TROSY-HSQC NMR) analysis of15N-Trp Gβγ identified well-dispersed signals for the individual Trp residue side chain and amide positions. Surprisingly, a wide range of signal intensities was observed in the spectrum, likely representing a range of backbone and side chain mobilities. The signal for GβW99 indole was very intense, suggesting a high level of mobility on the protein surface and molecular dynamics simulations indicate that GβW99 is highly mobile on the nanosecond timescale in comparison with other Gβ tryptophans. Binding of peptides and phosducin dramatically altered the mobility of GβW99 and GβW332 in the binding site and the chemical shifts at sites distant from the direct binding surface in distinct ways. In contrast, binding of Gαi1-GDP to Gβγ had relatively little effect on the spectrum and, most surprisingly, did not significantly alter Trp mobility at the subunit interface. This suggests the inactive heterotrimer in solution adopts a conformation with an open subunit interface a large percentage of the time. Overall, these data show that Gβγ subunits explore a range of conformations that can be exploited during molecular recognition by diverse binding partners.
Nanoparticles reveal that human cervicovaginal mucus is riddled with pores larger than viruses
Authors: Lai Samuel K. , Wang Ying-Ying , Hida Kaoru , Cone Richard , Hanes Justin
Published: December 2009

The mechanisms by which mucus helps prevent viruses from infecting mucosal surfaces are not well understood. We engineered non-mucoadhesive nanoparticles of various sizes and used them as probes to determine the spacing between mucin fibers (pore sizes) in fresh undiluted human cervicovaginal mucus (CVM) obtained from volunteers with healthy vaginal microflora. We found that most pores in CVM have diameters significantly larger than human viruses (average pore size 340 ± 70 nm; range approximately 50–1800 nm). This mesh structure is substantially more open than the 15–100-nm spacing expected assuming mucus consists primarily of a random array of individual mucin fibers. Addition of a nonionic detergent to CVM caused the average pore size to decrease to 130 ± 50 nm. This suggests hydrophobic interactions between lipid-coated “naked” protein regions on mucins normally cause mucin fibers to self-condense and/or bundle with other fibers, creating mucin “cables” at least three times thicker than individual mucin fibers. Although the native mesh structure is not tight enough to trap most viruses, we found that herpes simplex virus (approximately 180 nm) was strongly trapped in CVM, moving at least 8,000-fold slower than non-mucoadhesive 200-nm nanoparticles. This work provides an accurate measurement of the pore structure of fresh, hydrated ex vivo CVM and demonstrates that mucoadhesion, rather than steric obstruction, may be a critical protective mechanism against a major sexually transmitted virus and perhaps other viruses.
Complex regulation of the TIR1/AFB family of auxin receptors
Authors: Parry G. , Calderon-Villalobos L. I. , Prigge M. , Peret B. , Dharmasiri S. , Itoh H. , Lechner E. , Gray W. M. , Bennett M. , Estelle M.
Published: December 2009

Auxin regulates most aspects of plant growth and development. The hormone is perceived by the TIR1/AFB family of F-box proteins acting in concert with the Aux/IAA transcriptional repressors.
Arabidopsis
plants that lack members of the TIR1/AFB family are auxin resistant and display a variety of growth defects. However, little is known about the functional differences between individual members of the family. Phylogenetic studies reveal that the TIR1/AFB proteins are conserved across land plant lineages and fall into four clades. Three of these subgroups emerged before separation of angiosperms and gymnosperms whereas the last emerged before the monocot-eudicot split. This evolutionary history suggests that the members of each clade have distinct functions. To explore this possibility in
Arabidopsis
, we have analyzed a range of mutant genotypes, generated promoter swap transgenic lines, and performed in vitro binding assays between individual TIR1/AFB and Aux/IAA proteins. Our results indicate that the TIR1/AFB proteins have distinct biochemical activities and that TIR1 and AFB2 are the dominant auxin receptors in the seedling root. Further, we demonstrate that
TIR1
,
AFB2
, and
AFB3
, but not
AFB1
exhibit significant posttranscriptional regulation. The microRNA
miR393
is expressed in a pattern complementary to that of the auxin receptors and appears to regulate
TIR1
/
AFB
expression. However our data suggest that this regulation is complex. Our results suggest that differences between members of the auxin receptor family may contribute to the complexity of auxin response.
Secretagogin is a Ca
2+
-binding protein specifying subpopulations of telencephalic neurons
Authors: Mulder Jan , Zilberter Misha , Spence Lauren , Tortoriello Giuseppe , Uhlén Mathias , Yanagawa Yuchio , Aujard Fabienne , Hökfelt Tomas , Harkany Tibor
Published: December 2009

The Ca
2+
-binding proteins (CBPs) parvalbumin, calbindin, and calretinin are phenotypic markers of terminally differentiated neurons in the adult brain. Although subtle phylogenetic variations in the neuronal distribution of these CBPs may occur, morphologically and functionally diverse subclasses of interneurons harbor these proteins in olfactory and corticolimbic areas. Secretagogin (scgn) is a recently cloned CBP from pancreatic β and neuroendocrine cells. We hypothesized that scgn is expressed in the mammalian brain. We find that scgn is a marker of neuroblasts commuting in the rostral migratory stream. Terminally differentiated neurons in the olfactory bulb retain scgn expression, with scgn being present in periglomerular cells and granular layer interneurons. In the corticolimbic system, scgn identifies granule cells distributed along the dentate gyrus, indusium griseum, and anterior hippocampal continuation emphasizing the shared developmental origins, and cytoarchitectural and functional similarities of these neurons. We also uncover unexpected phylogenetic differences in scgn expression, since this CBP is restricted to primate cholinergic basal forebrain neurons. Overall, we characterize scgn as a neuron-specific CBP whose distribution identifies neuronal subtypes and hierarchical organizing principles in the mammalian brain.
Multiple chromatin-bound protein kinases assemble factors that regulate insulin gene transcription
Authors: Lawrence Michael C. , Shao Chunli , McGlynn Kathleen , Naziruddin Bashoo , Levy Marlon F. , Cobb Melanie H.
Published: December 2009

During the onset of diabetes, pancreatic β cells become unable to produce sufficient insulin to maintain blood glucose within the normal range. Proinflammatory cytokines have been implicated in impaired β cell function. To understand more about the molecular events that reduce insulin gene transcription, we examined the effects of hyperglycemia alone and together with the proinflammatory cytokine interleukin-1β (IL-1β) on signal transduction pathways that regulate insulin gene transcription. Exposure to IL-1β in fasting glucose activated multiple protein kinases that associate with the insulin gene promoter and transiently increased insulin gene transcription in β cells. In contrast, cells exposed to hyperglycemic conditions were sensitized to the inhibitory actions of IL-1β. Under these conditions, IL-1β caused the association of the same protein kinases, but a different combination of transcription factors with the insulin gene promoter and began to reduce transcription within 2 h; stimulatory factors were lost, RNA polymerase II was lost, and inhibitory factors were bound to the promoter in a kinase-dependent manner.
Focus Group Study of Hand Hygiene Practice among Healthcare Workers in a Teaching Hospital in Toronto, Canada
Authors: Jang Ti-Hyun , Wu Samantha , Kirzner Debra , Moore Christine , Youssef Gomana , Tong Agnes , Lourenco Jenny , Stewart Robyn B. , McCreight Liz J. , Green Karen , McGeer Allison
Published: December 2009

Objective.

To understand the behavioral determinants of hand hygiene in our hospital.

Design.

Qualitative study based on 17 focus groups.

Setting.

Mount Sinai Hospital, an acute care tertiary hospital affiliated with the University of Toronto.

Participants.

We recruited 153 healthcare workers (HCWs) representing all major patient care job categories.

Methods.

Focus group discussions were transcribed verbatim. Thematic analysis was independently conducted by 3 investigators.

Results.

Participants reported that the realities of their workload (eg, urgent care and interruptions) make complete adherence to hand hygiene impossible. The guidelines were described as overly conservative, and participants expressed that their judgement is adequate to determine when to perform hand hygiene. Discussions revealed gaps in knowledge among participants; most participants expressed interest in more information and education. Participants reported self-protection as the primary reason for the performance of hand hygiene, and many admitted to prolonged glove use because it gave them a sense of protection. Limited access to hand hygiene products was a source of frustration, as was confusion related to hospital equipment as potential vehicles for transmission of infection. Participants said that they noticed other HCWs' adherence and reported that others HCWs' hygiene practices influenced their own attitudes and practices. In particular, HCWs perceive physicians as role models; physicians, however, do not see themselves as such.

Conclusions.

Our results confirm previous findings that hand hygiene is practiced for personal protection, that limited access to supplies is a barrier, and that role models and a sense of team effort encourage hand hygiene. Educating HCWs on how to manage workload with guideline adherence and addressing contaminated hospital equipment may improve compliance.
The β Subunit of the Heterotrimeric G Protein Triggers theKluyveromyces lactisPheromone Response Pathway in the Absence of the γ Subunit
Authors: Navarro-Olmos Rocío , Kawasaki Laura , Domínguez-Ramírez Lenin , Ongay-Larios Laura , Pérez-Molina Rosario , Coria Roberto
Published: December 2009

The Kluyveromyces lactis heterotrimeric G protein is a canonical Gαβγ complex; however, in contrast to Saccharomyces cerevisiae, where the Gγ subunit is essential for mating, disruption of the KlGγ gene yielded cells with almost intact mating capacity. Expression of a nonfarnesylated Gγ, which behaves as a dominant-negative in S. cerevisiae, did not affect mating in wild-type and ΔGγ cells of K. lactis. In contrast to the moderate sterility shown by the single ΔKlGα, the double ΔKlGα ΔKlGγ mutant displayed full sterility. A partial sterile phenotype of the ΔKlGγ mutant was obtained in conditions where the KlGβ subunit interacted defectively with the Gα subunit. The addition of a CCAAX motif to the C-end of KlGβ, partially suppressed the lack of both KlGα and KlGγ subunits. In cells lacking KlGγ, the KlGβ subunit cofractionated with KlGα in the plasma membrane, but in the ΔKlGα ΔKlGγ strain was located in the cytosol. When the KlGβ-KlGα interaction was affected in the ΔKlGγ mutant, most KlGβ fractionated to the cytosol. In contrast to the generic model of G-protein function, the Gβ subunit of K. lactis has the capacity to attach to the membrane and to activate mating effectors in absence of the Gγ subunit.
Compartment-specific Synthesis of Phosphatidylethanolamine Is Required for Normal Heavy Metal Resistance
Authors: Gulshan Kailash , Shahi Puja , Moye-Rowley W. Scott
Published: December 2009

Control of lipid composition of membranes is crucial to ensure normal cellular functions. Saccharomyces cerevisiae has two different phosphatidylserine decarboxylase enzymes (Psd1 and Psd2) that catalyze formation of phosphatidylethanolamine. The mitochondrial Psd1 provides roughly 70% of the phosphatidylethanolamine (PE) biosynthesis in the cell with Psd2 carrying out the remainder. Here, we demonstrate that loss of Psd2 causes cells to acquire sensitivity to cadmium even though Psd1 remains intact. This cadmium sensitivity results from loss of normal activity of a vacuolar ATP-binding cassette transporter protein called Ycf1. Measurement of phospholipid levels indicates that loss of Psd2 causes a specific reduction in vacuolar membrane PE levels, whereas total PE levels are not significantly affected. The presence of a phosphatidylinositol transfer protein called Pdr17 is required for Psd2 function and normal cadmium tolerance. We demonstrate that Pdr17 and Psd2 form a complex in vivo that seems essential for maintenance of vacuolar PE levels. Finally, we refine the localization of Psd2 to the endosome arguing that this enzyme controls vacuolar membrane phospholipid content by regulating phospholipids in compartments that will eventually give rise to the vacuole. Disturbance of this regulation of intracellular phospholipid balance leads to selective loss of membrane protein function in the vacuole.
RNAsnoop: efficient target prediction for H/ACA snoRNAs
Authors: Tafer Hakim , Kehr Stephanie , Hertel Jana , Hofacker Ivo L. , Stadler Peter F.
Published: December 2009

Motivation: Small nucleolar RNAs are an abundant class of non-coding RNAs that guide chemical modifications of rRNAs, snRNAs and some mRNAs. In the case of many ‘orphan’ snoRNAs, the targeted nucleotides remain unknown, however. The box H/ACA subclass determines uridine residues that are to be converted into pseudouridines via specific complementary binding in a well-defined secondary structure configuration that is outside the scope of common RNA (co-)folding algorithms.

Results:  RNAsnoop implements a dynamic programming algorithm that computes thermodynamically optimal H/ACA-RNA interactions in an efficient scanning variant. Complemented by an support vector machine (SVM)-based machine learning approach to distinguish true binding sites from spurious solutions and a system to evaluate comparative information, it presents an efficient and reliable tool for the prediction of H/ACA snoRNA target sites. We apply RNAsnoop to identify the snoRNAs that are responsible for several of the remaining ‘orphan’ pseudouridine modifications in human rRNAs, and we assign a target to one of the five orphan H/ACA snoRNAs in Drosophila.

Availability: The C source code of RNAsnoop is freely available at http://www.tbi.univie.ac.at/∼htafer/RNAsnoop

Contact:  htafer@tbi.univie.ac.at

Supplementary information:  Supplementary data are available at Bioinformatics online.
Pleasure as Unconstrained Movement in Renaissance Literary Aesthetics
Authors: Langer Ullrich
Published: December 2009

In this essay I show that the pleasure provided by the poem as an imaginary landscape, as evidenced in rhetorical theory (Quintilian's analysis of
varietas
in Virgil's
Georgics
), and in exemplary poems by Du Bellay (‘Romae descriptio’) and Ronsard (‘Elegie à Louis Des Masures’), can be identified as that of unconstrained movement. Aristotle's definition of pleasure as unimpeded activity of our natural faculties in the
Nicomachean Ethics
captures the aesthetic attraction yielded by descriptive variety and links it to the ethical. Poussin's heroic landscape painting is an avatar of this neo-classical, humanist pleasure.
Predicting the Unpredictable
Authors: Eijkemans Marinus J. C. , van Houdenhoven Mark , Nguyen Tien , Boersma Eric , Steyerberg Ewout W. , Kazemier Geert
Published: December 2009

Background

: Routine predictions made by surgeons or historical mean durations have only limited capacity to predict operating room (OR) time. The authors aimed to devise a prediction model using the surgeon's estimate and characteristics of the surgical team, the operation, and the patient.

Methods

: Seventeen thousand four hundred twelve consecutive, elective operations from the general surgical department in an academic hospital were analyzed. The outcome was OR time, and the potential predictive factors were surgeon's estimate, number of planned procedures, number and experience of surgeons and anesthesiologists, patient's age and sex, number of previous hospital admissions, body mass index, and eight cardiovascular risk factors. Linear mixed modeling on the logarithm of the total OR time was performed.

Results

: Characteristics of the operation and the team had the largest predictive performance, whereas patient characteristics had a modest but distinct effect on OR time: operations were shorter for patients older than 60 yr, and higher body mass index was associated with longer OR times. The surgeon's estimate had an independent and substantial contribution to the prediction, and the final model explained 27% of the residual variation in log (OR time). Using the prediction model instead of the surgeon's prediction based on historical averages would reduce shorter-than-predicted and longer-than-predicted OR time by 2.8 and 6.6 min per case (a relative reduction of 12 and 25%, respectively), assessed on independent validation data.

Conclusions

: Detailed information on the operative session, the team, and the patient substantially improves the prediction of OR times, but the surgeon's estimate remains important. The prediction model may be used in OR scheduling.
Effects of Prone and Reverse Trendelenburg Positioning on Ocular Parameters
Authors: Grant Geordie P. , Szirth Bernard C. , Bennett Henry L. , Huang Sophia S. , Thaker Rajesh S. , Heary Robert F. , Turbin Roger E.
Published: December 2009

Background

: In a pilot study of awake volunteers, intraocular pressure (IOP), choroid layer thickness, and optic nerve diameter were shown to increase in the prone position over 5 h with a nonsignificant trend of attenuation using a 4-degree increase of table inclination. These effects have previously not been isolated from anesthetic and fluid administration over a prolonged period, using an adequate sample size.

Methods

: After institutional review board approval, 10 healthy volunteers underwent IOP measurement (Tono-Pen XL, Medtronic Solan, Jacksonville, FL) as well as choroidal thickness and optic nerve diameter assessment (Sonomed B-1000, Sonomed, Inc., Lake Success, NY, or the I System-ABD, Innovative Imaging, Inc., Sacramento, CA) on a Jackson table (Orthopedic Systems, Inc., Union City, CA), during 5 h horizontal prone and 5 h 4-degree reverse Trendelenburg positioning. Measurements were assessed as initial supine, initial prone, and hourly thereafter. Vital signs were recorded at each position and time point.

Results

: IOP, choroidal thickness, and optic nerve diameter were observed to increase with time in the prone position. A small degree of reverse Trendelenburg attenuated the increase in choroidal thickness but not IOP or optic nerve diameter.

Conclusions

: Prolonged prone positioning increases IOP, choroid layer thickness, and optic nerve diameter independent of anesthetics and intravenous fluid infusion and 4 degrees of table inclination (15 cm of head to foot vertical disparity) may not attenuate these effects.
Cerebrospinal Fluid and Spinal Cord Distribution of Hyperbaric Bupivacaine and Baclofen during Slow Intrathecal Infusion in Pigs
Authors: Flack Sean H. , Bernards Christopher M.
Published: December 2009

Background

Despite the widespread use of implanted pumps for continuous intrathecal drug delivery, there have been no studies aimed at defining the effect of baricity and posture on drug distribution in the cerebrospinal fluid and spinal cord during the very slow infusion rates typically used for chronic intrathecal drug administration.

Methods

Intrathecal microdialysis probes were placed at six points along the neuraxis in both the anterior and posterior intrathecal space of anesthetized pigs to permit cerebrospinal fluid sampling. Animals were then positioned either vertically or horizontally (prone), and a hyperbaric solution containing bupivacaine (7.5 mg/ml) and baclofen (2 mg/ml) was infused at 20 microl/h for 6 h, while the cerebrospinal fluid was collected for measurement of drug concentration. At the end of the experiment, the animals were killed, and the spinal cord was removed and divided into 1-cm sections that were further divided into anterior and posterior portions for measurement of drug concentration.

Results

Bupivacaine and baclofen distribution was biased caudally in the vertical group and cephalad in the horizontal group. Drug concentration decreased rapidly in the cerebrospinal fluid and spinal cord as a function of distance from the site of administration in both groups, resulting in most drugs being located in very close proximity to the site of infusion.

Conclusion

Even at very slow infusion rates, drug distribution within the cerebral spinal fluid and spinal cord are affected by baricity/posture. These findings suggest that patient position and solution baricity may be important clinical factors determining the distribution and ultimate efficacy of chronic intrathecal drug infusions.
Acquisition of Critical Intraoperative Event Management Skills in Novice Anesthesiology Residents by Using High-fidelity Simulation-based Training
Authors: Park Christine S. , Rochlen Lauryn R. , Yaghmour Edward , Higgins Nicole , Bauchat Jeanette R. , Wojciechowski Kyle G. , Sullivan John T. , McCarthy Robert J.
Published: December 2009

Background

Early acquisition of critical competencies by novice anesthesiology residents is essential for patient safety, but traditional training methods may be insufficient. The purpose of this study was to determine the effectiveness of high-fidelity simulation training of novice residents in the initial management of critical intraoperative events.

Methods

Twenty-one novice residents participated in this 6-week study. Three hypoxemia and three hypotension scenarios were developed and corresponding checklists were validated. Residents were tested in all scenarios at baseline (0 weeks) and divided into two groups, using a randomized crossover study design. Group 1 received simulation-based training in hypoxemic events, whereas Group 2 was trained in hypotensive events. After intermediate (3 weeks) testing in all scenarios, the groups switched to receive training in the other critical event. Final testing occurred at 6 weeks. Raters blinded to subject identity, group assignment, and test date scored videotaped performances by using checklists. The primary outcome measure was composite scores for hypoxemia and hypotension scenarios, which were compared within and between groups.

Results

Baseline performance between groups was similar. At the intermediate evaluation, the mean hypoxemia score was higher in Group 1 compared with Group 2 (65.5% vs. 52.4%, 95% CI of difference 6.3-19.9, P < 0.003). Conversely, Group 2 had a higher mean hypotension score (67.4% vs. 45.5%, 95% CI of difference 14.6-29.2, P < 0.003). At Week 6, the scores between groups did not differ.

Conclusions

Event-specific, simulation-based training resulted in superior performance in scenarios compared with traditional training and simulation-based training in an alternate event.
Introduction of Complementary Feeding in 5 European Countries
Authors: Schiess Sonia , Grote Veit , Scaglioni Silvia , Luque Veronica , Martin Francoise , Stolarczyk Anna , Vecchi Fiammetta , Koletzko Berthold ,   European Childhood Obesity Project
Published: December 2009

Objectives:

Little is known about the practice of introducing complementary feeding across Europe. We aim at describing times of solid introduction in healthy infants in 5 European countries.

Materials and Methods:

Between October 2002 and June 2004, 1678 healthy term infants were either breast‐fed (BF) for at least 4 months (n = 588) or study formula–fed (FF) (n = 1090) with different protein contents. Three‐day‐weighed food protocols were obtained at ages 1, 2, 3, 4, 5, 6, 7, 8, 9, and 12 completed months.

Results:

Solids were introduced earlier in FF infants (median 19 weeks, interquartile range 17–21) than BF infants (median 21 weeks, interquartile range 19–24). Some 37.2% of FF infants and 17.2% of BF infants received solid foods at 4 completed months, which is earlier than recommended in Europe. Solids had been introduced at 7 completed months in 99.3% of FF infants and 97.7% of BF infants, respectively. Belgium had the highest percentage of solids feeding in FF infants at 3 (15.8%) and 4 (55.6%) completed months, and in BF infants at 4 (43%) and 5 (84.8%) completed months. Multiple regression showed low maternal age, low education level, and maternal smoking to predictors an early introduction of solids at 3 and 4 completed months.

Conclusions:

Complementary feeding is introduced earlier than recommended in a sizeable number of infants, particularly among FF infants. Country‐ and population‐specific approaches to adequately inform parents should be explored.
Enteral Nutrient Supply for Preterm Infants: Commentary From the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition
Authors: Agostoni C , Buonocore G , Carnielli VP , De Curtis M , Darmaun D , Decsi T , Domellöf M , Embleton ND , Fusch C , Genzel‐Boroviczeny O , Goulet O , Kalhan SC , Kolacek S , Koletzko B , Lapillonne A , Mihatsch W , Moreno L , Neu J , Poindexter B , Puntis J , Putet G , Rigo J , Riskin A , Salle B , Sauer P , Shamir R , Szajewska H , Thureen P , Turck D , van Goudoever JB , Ziegler EE ,   ESPGHAN Committee on Nutrition
Published: December 2009

The number of surviving children born prematurely has increased substantially during the last 2 decades. The major goal of enteral nutrient supply to these infants is to achieve growth similar to foetal growth coupled with satisfactory functional development. The accumulation of knowledge since the previous guideline on nutrition of preterm infants from the Committee on Nutrition of the European Society of Paediatric Gastroenterology and Nutrition in 1987 has made a new guideline necessary. Thus, an ad hoc expert panel was convened by the Committee on Nutrition of the European Society of Paediatric Gastroenterology, Hepatology, and Nutrition in 2007 to make appropriate recommendations. The present guideline, of which the major recommendations are summarised here (for the full report, see http://links.lww.com/A1480), is consistent with, but not identical to, recent guidelines from the Life Sciences Research Office of the American Society for Nutritional Sciences published in 2002 and recommendations from the handbook Nutrition of the Preterm Infant. Scientific Basis and Practical Guidelines, 2nd ed, edited by Tsang et al, and published in 2005. The preferred food for premature infants is fortified human milk from the infant's own mother, or, alternatively, formula designed for premature infants. This guideline aims to provide proposed advisable ranges for nutrient intakes for stable‐growing preterm infants up to a weight of approximately 1800 g, because most data are available for these infants. These recommendations are based on a considered review of available scientific reports on the subject, and on expert consensus for which the available scientific data are considered inadequate.
Early‐onset Crohn Disease Is Associated With Male Sex and a Polymorphism in the IL‐6 Promoter
Authors: Sagiv‐Friedgut Keren , Karban Amir , Weiss Batya , Shaoul Ron , Shamir Raanan , Bujanover Yoram , Reif Shimon , Boaz Mona , Shani Inbar , Levine Arie , Leshinsky‐Silver Esther
Published: December 2009

Aims:

Pediatric onset of Crohn disease (CD) is characterized by male sex predominance while adult‐onset disease demonstrates female sex predominance. It has been postulated that this phenomenon may be genetically determined or due to an effect of estrogen on age of onset. Interleukin (IL)‐6 modulates the TH17 pathway, and the IL‐6 promoter is modulated by estrogen, possibly linking genetically determined inflammation and the presence of estrogen. The aim of our study was to investigate whether differences in IL‐6 promoter genotype could explain male sex in earlier disease onset.

Patients and Methods:

We genotyped 333 patients with CD and 100 controls, 162 pediatric‐onset patients (age of onset 18 years and younger) for the IL‐6‐174 polymorphic site. Genotype, sex, and age of onset were compared.

Results:

Males with IL‐6‐174GG genotype (the wild‐type allele) had an increased risk for a younger age of onset compared to males with IL‐6‐174GC or CC genotype (G → C genotype), hazard ratio (HR) 1.49, P = 0.02, 95% confidence interval (CI) 1.07–2.09. Females with GG genotype were not found to have an increased risk for a younger age of onset compared with females with G → C genotype, HR 1.01, P = 0.96, 95% CI 0.72–1.41.

Conclusions:

Males with IL‐6‐174GG genotype are prone to develop CD at a younger age than males with the IL‐6‐174G → C genotype. Our study suggests that age of onset may be modified by the IL‐6‐174GG genotype and this modification is sex dependent. This may be due to increased transcription of IL‐6, an effect that may be repressed by estrogen in females.
Alagille Syndrome and Liver Transplantation
Authors: Kamath Binita M , Schwarz Kathleen B , Hadžić Nedim
Published: December 2009

Alagille syndrome is a multisystem disorder in which progressive liver disease with persistent cholestasis and dramatic pruritus often warrant consideration for liver transplantation. The most important part of the transplant assessment is evaluation of the cardiac and renal involvement. Preoperatively, cardiac performance often must be tested with dynamic stress tests, mimicking hemodynamic changes during liver transplant. Many aspects of the syndrome including cholestasis, pruritus, and hypercholesterolemia improve posttransplant, but short stature is rarely significantly affected. One‐ and 5‐year patient and graft survival after liver transplant is comparable to other elective indications, but effects of long‐term immunosuppressants on evolution of other components of the syndrome, including vascular, bone, and renal disease, remain largely unknown.
Fitts' law is not continuous in reciprocal aiming
Authors: Huys Raoul , Fernandez Laure , Bootsma Reinoud J. , Jirsa Viktor K.
Published: December 2009

It takes longer to accomplish difficult tasks than easy ones. In the context of motor behaviour, Fitts' famous law states that the time needed to successfully execute an aiming movement increases linearly with task difficulty. While Fitts' explicit formulation has met criticism, the relation between task difficulty and movement time is invariantly portrayed as continuous. Here, we demonstrate that Fitts' law is discontinuous in reciprocal aiming owing to a transition in operative motor control mechanisms with increasing task difficulty. In particular, rhythmic movements are implemented in easy tasks and discrete movements in difficult ones. How movement time increases with task difficulty differs in both movement types. It appears, therefore, that the human nervous system abruptly engages a different control mechanism when task difficulty increases.
Diversity trends and their ontogenetic basis: an exploration of allometric disparity in rodents
Authors: Wilson Laura A. B. , Sánchez-Villagra Marcelo R.
Published: December 2009

It has been hypothesized that most morphological evolution occurs by allometric differentiation. Because rodents encapsulate a phenomenal amount of taxonomic diversity and, among several clades, contrasting levels of morphological diversity, they represent an excellent subject to address the question: how variable are allometric patterns during evolution? We investigated the influence of phylogenetic relations and ecological factors on the results of the first quantification of allometric disparity among rodents by exploring allometric space, a multivariate morphospace here derived from, and encapsulating all, the ontogenetic trajectories of 34 rodent species from two parallel phylogenetic radiations. Disparity was quantified using angles between ontogenetic trajectories for different species and clades. We found an overlapping occupation of allometric space by muroid and hystricognath species, revealing both clades possess similar abilities to evolve in different directions of phenotypic space, and anatomical diversity does not act to constrain the labile nature of allometric patterning. Morphological features to enable efficient processing of food serve to group rodents in allometric space, reflecting the importance of convergent morphology, rather than shared evolutionary history, in the generation of allometric patterns. Our results indicate that the conserved level of morphological integration found among primates cannot simply be extended to all mammals.