bluuebunny/crossref_metadata_2025 huggingface dataset:
The inherent instability of mutant p53 is alleviated by Mdm2 or p16INK4a loss
Authors: Terzian Tamara , Suh Young-Ah , Iwakuma Tomoo , Post Sean M. , Neumann Manja , Lang Gene A. , Van Pelt Carolyn S. , Lozano Guillermina
Published: May 2008

The p53 tumor suppressor is often disrupted in human cancers by the acquisition of missense mutations. We generated mice with a missense mutation at codon 172 that mimics the p53R175H hot spot mutation in human cancer. p53 homozygous mutant mice have unstable mutant p53 in normal cells and stabilize mutant p53 in some but not all tumors. To investigate the significance of these data, we examined the regulation of mutant p53 stability by Mdm2, an E3 ubiquitin ligase that targets p53 for degradation, and p16INK4a, a member of the Rb tumor suppressor pathway. Mice lacking Mdm2 or p16INK4a stabilized mutant p53, and revealed an earlier age of tumor onset than p53 mutant mice and a gain-of-function metastatic phenotype. Analysis of tumors from p53 homozygous mutant mice with stable p53 revealed defects in the Rb pathway. Additionally, ionizing radiation stabilizes wild-type and mutant p53. Thus, the stabilization of mutant p53 is not a given but it is a prerequisite for its gain-of-function phenotype. Since mutant p53 stability mimics that of wild-type p53, these data indicate that drugs aimed at activating wild-type p53 will also stabilize mutant p53 with dire consequences.
Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex
Authors: Kajimura Shingo , Seale Patrick , Tomaru Takuya , Erdjument-Bromage Hediye , Cooper Marcus P. , Ruas Jorge L. , Chin Sherry , Tempst Paul , Lazar Mitchell A. , Spiegelman Bruce M.
Published: May 2008

Brown fat is a specialized tissue that can dissipate energy and counteract obesity through a pattern of gene expression that greatly increases mitochondrial content and uncoupled respiration. PRDM16 is a zinc-finger protein that controls brown fat determination by stimulating brown fat-selective gene expression, while suppressing the expression of genes selective for white fat cells. To determine the mechanisms regulating this switching of gene programs, we purified native PRDM16 protein complexes from fat cells. We show here that the PRDM16 transcriptional holocompex contains C-terminal-binding protein-1 (CtBP-1) and CtBP-2, and this direct interaction selectively mediates the repression of white fat genes. This repression occurs through recruiting a PRDM16/CtBP complex onto the promoters of white fat-specific genes such as resistin, and is abolished in the genetic absence of CtBP-1 and CtBP-2. In turn, recruitment of PPAR-γ-coactivator-1α (PGC-1α) and PGC-1β to the PRDM16 complex displaces CtBP, allowing this complex to powerfully activate brown fat genes, such as PGC-1α itself. These data show that the regulated docking of the CtBP proteins on PRDM16 controls the brown and white fat-selective gene programs.
Diverse functions of WD40 repeat proteins in histone recognition: Figure 1.
Authors: Suganuma Tamaki , Pattenden Samantha G. , Workman Jerry L.
Published: May 2008

WD40 repeat proteins have been shown to bind the histone H3 tail at the center of their β-propeller structure. In contrast, in this issue of Genes & Development, Song and colleagues (pp. 1313–1318) demonstrate that the WD40 repeat protein p55 binds a structured region of H4 through a novel binding pocket on the side of β-propeller, illustrating a diversity of histone recognition by WD40 repeat proteins.
Does control of mutant p53 by Mdm2 complicate cancer therapy?: Figure 1.
Authors: Prives Carol , White Eileen
Published: May 2008

Missense mutant forms of p53 are expressed at high levels in some human cancers and may contribute to oncogenesis. In this issue of Genes & Development, Terzian and colleagues (pp. 1337–1344) describe a mutant p53 knock-in mouse in which normal tissues and some tumors have low levels of mutant p53 protein unless Mdm2 or p16INK4A are absent. Once stabilized, mutant p53 promotes metastasis. Therefore, therapies that release p53 from Mdm2 might have unwanted consequences when cells have sustained a mutation in p53.
Molecular determinants of brown adipocyte formation and function: Figure 1.
Authors: Farmer Stephen R.
Published: May 2008

Humans contain essentially two types of adipose tissue: brown adipose tissue (BAT) and white adipose tissue (WAT). The function of WAT is to store fat while that of BAT is to burn fat for heat production. A potential strategy to combat obesity and its related disorders is to induce the conversion of WAT into BAT. In this issue of Genes & Development, Kajimura and colleagues (pp. 1397–1409) have identified a mechanism by which PRDM16, the principal regulator of brown adipocyte formation and function, can simultaneously induce BAT gene expression, while suppressing WAT gene expression. The studies suggest that PRDM16 and its associated coregulators PPARγ coactivator-1α (PGC-1α) and C-terminal-binding protein 1/2 (CtBP1/2), which control the switch from WAT to BAT, are potential targets for development of obesity-related therapeutics.
Control of final seed and organ size by the DA1 gene family in Arabidopsis thaliana
Authors: Li Yunhai , Zheng Leiying , Corke Fiona , Smith Caroline , Bevan Michael W.
Published: May 2008

Although the size of an organism is a defining feature, little is known about the mechanisms that set the final size of organs and whole organisms. Here we describe Arabidopsis DA1, encoding a predicted ubiquitin receptor, which sets final seed and organ size by restricting the period of cell proliferation. The mutant protein encoded by the da1-1 allele has a negative activity toward DA1 and a DA1-related (DAR) protein, and overexpression of a da1-1 cDNA dramatically increases seed and organ size of wild-type plants, identifying this small gene family as important regulators of seed and organ size in plants.
NMD is essential for hematopoietic stem and progenitor cells and for eliminating by-products of programmed DNA rearrangements
Authors: Weischenfeldt Joachim , Damgaard Inge , Bryder David , Theilgaard-Mönch Kim , Thoren Lina A. , Nielsen Finn Cilius , Jacobsen Sten Eirik W. , Nerlov Claus , Porse Bo Torben
Published: May 2008

Nonsense-mediated mRNA decay (NMD) is a post-transcriptional surveillance process that eliminates mRNAs containing premature termination codons (PTCs). NMD has been hypothesized to impact on several aspects of cellular function; however, its importance in the context of a mammalian organism has not been addressed in detail. Here we use mouse genetics to demonstrate that hematopoietic-specific deletion of Upf2, a core NMD factor, led to the rapid, complete, and lasting cell-autonomous extinction of all hematopoietic stem and progenitor populations. In contrast, more differentiated cells were only mildly affected in Upf2-null mice, suggesting that NMD is mainly essential for proliferating cells. Furthermore, we show that UPF2 loss resulted in the accumulation of nonproductive rearrangement by-products from the Tcrb locus and that this, as opposed to the general loss of NMD, was particularly detrimental to developing T-cells. At the molecular level, gene expression analysis showed that Upf2 deletion led to a profound skewing toward up-regulated mRNAs, highly enriched in transcripts derived from processed pseudogenes, and that NMD impacts on regulated alternative splicing events. Collectively, our data demonstrate a unique requirement of NMD for organismal survival.
The Potato-Specific Apyrase Is Apoplastically Localized and Has Influence on Gene Expression, Growth, and Development
Authors: Riewe David , Grosman Lukasz , Fernie Alisdair R. , Wucke Cornelia , Geigenberger Peter
Published: May 2008

Apyrases hydrolyze nucleoside triphosphates and diphosphates and are found in all eukaryotes and a few prokaryotes. Although their enzymatic properties have been well characterized, relatively little is known regarding their subcellular localization and physiological function in plants. In this study, we used reverse genetic and biochemical approaches to investigate the role of potato (Solanum tuberosum)-specific apyrase. Silencing of the apyrase gene family with RNA interference constructs under the control of the constitutive 35S promoter led to a strong decrease in apyrase activity to below 10% of the wild-type level. This decreased activity led to phenotypic changes in the transgenic lines, including a general retardation in growth, an increase in tuber number per plant, and differences in tuber morphology. Silencing of apyrase under the control of a tuber-specific promoter led to similar changes in tuber morphology; however, there were no direct effects of apyrase inhibition on tuber metabolism. DNA microarrays revealed that decreased expression of apyrase leads to increased levels of transcripts coding for cell wall proteins involved in growth and genes involved in energy transfer and starch synthesis. To place these results in context, we determined the subcellular localization of the potato-specific apyrase. Using a combination of approaches, we were able to demonstrate that this enzyme is localized to the apoplast. We describe the evidence that underlies both this fact and that potato-specific apyrase has a crucial role in regulating growth and development.
Circadian Timekeeping during Early Arabidopsis Development
Authors: Salomé Patrice A. , Xie Qiguang , McClung C. Robertson
Published: May 2008

The circadian coordination of organismal biology with the local temporal environment has consequences for fitness that may become manifest early in development. We directly explored the development of the Arabidopsis (Arabidopsis thaliana) clock in germinating seedlings by monitoring expression of clock genes. Clock function is detected within 2 d of imbibition (hydration of the dried seed). Imbibition is sufficient to synchronize individuals in a population in the absence of entraining cycles of light-dark or temperature, although light-dark and temperature cycles accelerate the appearance of rhythmicity and improve synchrony among individuals. Oscillations seen during the first 2 d following imbibition are dependent on the clock genes LATE ELONGATED HYPOCOTYL, TIMING OF CAB EXPRESSION1, ZEITLUPE, GIGANTEA, PSEUDO-RESPONSE REGULATOR7 (PRR7), and PRR9, although later circadian oscillations develop in mutants defective in each of these genes. In contrast to circadian rhythmicity, which developed under all conditions, amplitude was the only circadian parameter that demonstrated a clear response to the light environment; clock amplitude is low in the dark and high in the light. A circadian clock entrainable by temperature cycles in germinating etiolated seedlings may synchronize the buried seedling with the local daily cycles before emergence from the soil and exposure to light.
An Actin-Binding Protein, LlLIM1, Mediates Calcium and Hydrogen Regulation of Actin Dynamics in Pollen Tubes
Authors: Wang Huei-Jing , Wan Ai-Ru , Jauh Guang-Yuh
Published: May 2008

Actin microfilaments are crucial for polar cell tip growth, and their configurations and dynamics are regulated by the actions of various actin-binding proteins (ABPs). We explored the function of a lily (Lilium longiflorum) pollen-enriched LIM domain-containing protein, LlLIM1, in regulating the actin dynamics in elongating pollen tube. Cytological and biochemical assays verified LlLIM1 functioning as an ABP, promoting filamentous actin (F-actin) bundle assembly and protecting F-actin against latrunculin B-mediated depolymerization. Overexpressed LlLIM1 significantly disturbed pollen tube growth and morphology, with multiple tubes protruding from one pollen grain and coaggregation of FM4-64-labeled vesicles and Golgi apparatuses at the subapex of the tube tip. Moderate expression of LlLIM1 induced an oscillatory formation of asterisk-shaped F-actin aggregates that oscillated with growth period but in different phases at the subapical region. These results suggest that the formation of LlLIM1-mediated overstabilized F-actin bundles interfered with endomembrane trafficking to result in growth retardation. Cosedimentation assays revealed that the binding affinity of LlLIM1 to F-actin was simultaneously regulated by both pH and Ca2+: LlLIM1 showed a preference for F-actin binding under low pH and low Ca2+ concentration. The potential functions of LlLIM1 as an ABP sensitive to pH and calcium in integrating endomembrane trafficking, oscillatory pH, and calcium circumstances to regulate tip-focused pollen tube growth are discussed.
Five-coordinate copper(II) complexes: crystal structures, spectroscopic properties and new extended structural pathways of [Cu(chelate)2
X]Y, where chelate = dpyam, phen and bipy; X = pseudohalide ligands
Authors: Youngme Sujittra , Phuengphai Pongthipun , Pakawatchai Chaveng , Kongsaeree Palangpon , Chaichit Narongsak
Published: May 2008

The crystal structures of four distortion isomers of the [Cu(chelate)2
X]+ cation, where chelate = 2,2-bipyridine (bipy), 1,10-phenanthroline (phen) and di-2-pyridylamine (dpyam), X = a pseudohalide ligand (NCO, NCS, N3 and C2N3), have been compared by scatterplot analysis with 25 [Cu(chelate)2
X]Y complexes of known crystal structure. The four new complexes [Cu(phen)2NCO]Br (1), [Cu(phen)2N3]BPh4·H2O (2), [Cu(dpyam)2(N3)]NO3·H2O (3) and [Cu(dpyam)2(N3)]ClO4 (4) involve a near regular square-based pyramidal stereochemistry (RSBP). The structures of complexes (1) and (2) are of the rare cases found for the phen analogue. Scatterplots of the 29 cation distortion isomers of the [Cu(chelate)2
X]Y series of complexes suggest that most of the 29 complexes lie on a common structural pathway, involving a mixture of the symmetric, C
2, and the asymmetric, non-C
2, in-plane modes of vibration of the CuN4N′ chromophore. Some datapoints are found to lie on extended routes The resulting structural pathways are consistent with the direct observation of the effect of the modes of vibration on the stereochemistries of the complexes. A comparison of the trends in the 29 datasets suggests a size effect of the phen, bipy and dpyam ligands.
Comparative experimental electron density and electron localization function study of thymidine based on 20 K X-ray diffraction data
Authors: Hübschle Christian B. , Dittrich Birger , Grabowsky Simon , Messerschmidt Marc , Luger Peter
Published: May 2008

From a high-resolution X-ray data set (sin θ/λ = 1.1 Å−1) measured at 20 K the electron-density distribution of the nucleoside thymidine was derived by a classical multipole refinement and by application of the invariom formalism. Owing to the presence of the heteroaromatic thymine ring system two invariom models were compared which considered the nearest and next-nearest neighbors for the invariom assignments. Differences between the two invariom models were small for the bond topological and atomic properties – about five times smaller than differences with the classical multipole refinement. Even the latter differences are in the uncertainty ranges which are commonly observed in experimental charge-density work and were found in molecular regions involved in intermolecular contacts. The application of the constrained wavefunction-fitting approach allowed the electron localization function (ELF) to be obtained from the experimental X-ray data, which was graphically represented and topologically analyzed. ELF basin populations were derived from experiment for the first time. The electron populations in the disynaptic valence basins were related quantitatively to bond orders.
Synthesis and structural characteristics of lithocholate triads: steroid-type channels occupied by spacer fragments
Authors: Rychlewska Urszula , Warżajtis Beata , Joachimiak Roman , Paryzek Zdzisław
Published: May 2008

Reported in this paper are the syntheses and X-ray investigations of C
2 symmetrical molecular A—B—A triads consisting of two steroid units (lithocholic acid or its methyl ester) joined together by linkers derived from bifunctional molecules such as terephthalic acid or N,N′-dicarboxypiperazine. Unlike their monomeric analogues, some of these compounds form inclusion complexes. All steroidal triads form crystals that are highly pseudo-centrosymmetric, in which the constituting molecules are held together either exclusively by van der Waals forces or form lattice inclusion complexes, with guest molecules hydrogen bonded to the host. The presence of carboxyl groups promotes the inclusion of pyridine molecules and the formation of the well known carboxylic acid...pyridine hydrogen bonds. Combined with pairwise face-to-face π-stacking between pyridine rings, these hydrogen-bond interactions lead to the formation of extended supramolecular tapes, analogous to polymers. The co-crystals of pyridine and a lithocholic acid triad undergo a symmetry-lowering phase transition from a P1 cell with Z = 1 to a P1 cell with Z = 2. The two structures are virtually the same, the two independent molecules in the larger cell being related by pseudo-translation. Changes in the type of spacer between two methyl lithocholate units from planar aromatic (terephthalic acid) to highly puckered aliphatic six-membered ring (N,N′-dicarboxypiperazine) bring about inclusion properties and changes in side-chain conformation in a crystal. Although the efficient packing of these highly elongated molecules is hindered, as indicated by low values of crystal density, ranging from 1.16 to 1.19 g cm−3, several very short C...O and H...H contacts are present in the crystals.
Experimental electron density study of ethylene oxide at 100 K
Authors: Grabowsky Simon , Weber Manuela , Buschmann Jürgen , Luger Peter
Published: May 2008

The experimental electron density of ethylene oxide was derived from a multipole refinement of 100 K X-ray data and complemented by density-functional calculations at experimental and optimized geometry. Atomic and bond-topological properties were derived using the atoms-in-molecules (AIM) formalism. The high strain in the three-membered ring molecule is mainly expressed by the high ellipticities of the three bonds in this ring, while the bond paths are only slightly bent for the C—C bond, but are virtually straight for the C—O bond.
Pharmacokinetics and therapeutic drug monitoring of antiretrovirals in pregnant women
Authors: Roustit Matthieu , Jlaiel Malik , Leclercq Pascale , Stanke‐Labesque Françoise
Published: May 2008

Highly active antiretroviral therapy is recommended for HIV‐infected pregnant women to prevent mother‐to‐child transmission. The specific physiological background induced by pregnancy leads to significant changes in maternal pharmacokinetics, suggesting potential variability in plasma concentrations of antiretrovirals during gestation. Therapeutic drug monitoring (TDM) of protease inhibitors (PIs) and non‐nucleoside reverse transcriptase inhibitors (NNRTIs) is recommended in certain situations, including pregnancy, but its systematic use in HIV‐infected pregnant women remains controversial. This review provides an update of the pharmacokinetic data available for PIs and NNRTIs in pregnant women and highlights the clinical interest of systematic TDM of certain antiretroviral drugs during pregnancy, including nevirapine, nelfinavir, saquinavir, indinavir and lopinavir.
Interleukin‐6 induces proliferation in adult spinal cord‐derived neural progenitors via the JAK2/STAT3 pathway with EGF‐induced MAPK phosphorylation
Authors: Kang M. K. , Kang S. K.
Published: May 2008

Abstract.  Introduction: In a previous study, we observed cell proliferation 3 days after spinal cord injury, and levels of interleukin‐6 (IL‐6) and epidermal growth factor (EGF) had significantly increased in the region of the injury. Objectives: The purpose of the new study described here was to evaluate the roles of IL‐6 and EGF after traumatic damage to the spinal cord having isolated neural progenitor cells (NPC) from adult mice. Methods and results: Evidence provided by the trypan blue dye exclusion assay, 5‐bromodeoxyuridine immunoreactivity and Western blot analysis indicated that IL‐6 and EGF induced proliferation of these spinal cord‐derived NPCs via phosphorylation of Janus‐activated kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) and mitogen‐activated protein kinases (MAPK), respectively. Combined treatment with IL‐6 and EGF accelerated proliferation of cells synergistically and phosphorylation of STAT3 and extracellular signal‐regulated kinase 1/2 (Erk1/2). Furthermore, AG490 and AG1478, JAK2 inhibitor and EGFR inhibitor, respectively, prevented the IL‐6‐ and EGF‐induced proliferation of the cells. Interestingly, IL‐6‐activated MAPKs but EGF did not influence JAK2/STAT3 activation; AG490 specifically inhibited IL‐6‐induced Erk1/2 phosphorylation without affecting IL‐6‐induced phosphorylation of Raf and MEK1/2. These results indicate that IL‐6 is directly involved in Erk1/2 activation via JAK2 and that Erk1/2 provides a signal bridge between the IL‐6‐induced JAK2/STAT3 pathway and EGF‐induced MAPK pathway. Conclusions: Our study is the first demonstration of IL‐6‐ and EGF‐stimulated proliferation of spinal cord progenitor cells via JAK2/STAT3 and MAPK signalling pathways. These pathways play key roles in repopulation and regeneration of spinal cord tissue after injury. It may represent novel therapeutic targets for pharmacological intervention in central nervous system disease, including spinal cord injury.
Toilet training in Turkey: the factors that affect timing and duration in different sociocultural groups
Authors: Koc I. , Camurdan A. D. , Beyazova U. , Ilhan M. N. , Sahin F.
Published: May 2008

Background  The aim of the present study was to determine the patterns of toilet training and the factors that may be related to its timing and duration and the approaches of different sociocultural groups within a developing country.

Methods  This cross‐sectional survey was performed on 745 children who live in three different sociocultural settlements. The factors that might have affected initiation and completion age and duration of toilet training were assessed with t‐test, ANOVA and logistic regression analysis.

Results  Mean initiation and completion ages were 22.05 ± 6.73, 28.05 ± 8.40 months respectively. The families living in rural and semi‐urban settlements, mothers educated for less than 5 years, unoccupied mothers, children living in houses which do not have a toilet inside, families who use washable diapers, who use Turkish style toilets and who use punishment methods started training earlier. In the infants whose mothers had an education over 12 years, completion age was later than others and the earliest completion age was seen in families who used punishment method. Mean duration needed to complete toilet training was 6.84 ± 7.16 months. The duration of training was longer in families living in rural and semi‐urban settlements, mothers educated for less than 5 years, unoccupied mothers, children living in houses which do not have a toilet inside, families who use washable diapers and when the initiation was before the child was 18 months old.

Conclusion  Toilet training shows differences among cultures. The age of initiation may be increased as the parents are educated better and a child‐orientated approach becomes more popular than the parent‐orientated approach.
Transition pathways for young people with complex disabilities: exploring the economic consequences
Authors: Knapp M. , Perkins M. , Beecham Jennifer , Dhanasiri S. , Rustin C.
Published: May 2008

Background  Disabled young people with complex needs face particular challenges when they reach adulthood and seek to move from school to employment or further education. There are potentially substantial personal and social costs arising from these challenges.

Methods  We sought evidence from recent UK research, policy and related literatures; undertook exploratory statistical analyses of birth cohort data; and analysed information provided by 30 disabled young people requiring high levels of practical and communication support.

Results  The personal, family and social costs that result from unsuccessful transition are substantial and wide‐ranging. Health service and local authority expenditure are important elements, but do not allow young people to achieve the educational or employment goals to which they aspire, resulting in considerable costs for the state, whether through missing opportunities to contribute to the economy or through dependence on welfare benefits.

Conclusions  The considerable sums currently spent on disabled children and young people are clearly not enough, or not deployed appropriately, to enable those who reach adulthood to fulfil their ambitions, or to meet government policy intentions for young people to achieve economic well‐being.
A model for predicting the emergence of dragonflies in a changing climate
Authors: RICHTER OTTO , SUHLING FRANK , MÜLLER OLE , KERN DIETRICH
Published: May 2008

1. Precise models for the phenology of different species are essential for predicting the potential effects of any temporal mismatch of life cycles with environmental parameters under different climate change scenarios. Here we investigated the effects of ambient water temperature on the onset and synchrony of emergence for a widespread European riverine dragonfly, Gomphus vulgatissimus.

2. Long‐term field data on the annual emergence from two rivers in northern Germany, and additional data from a laboratory experiment with different temperature regimes, were used to develop a model that predicted the onset of emergence by using mainly the temperature sum (degree days) as a parameter.

3. Model predictions of the onset of emergence fitted the observations well and could be transferred between localities. This was particularly so when weighting early winter temperature data by using a day length and a temperature‐response function, implying potential additional control mechanisms for the onset of emergence.

4. We simulated effects of different winter temperature regimes on the emergence curves in order to predict the effects of climate change. These indicated an acceleration of emergence by 6–7 days per 1 °C temperature increase, which is corroborated by the laboratory data and is in the upper range of data published for other dragonflies.
Estimation of nitrogen concentration and in vitro dry matter digestibility of herbage of warm‐season grass pastures from canopy hyperspectral reflectance measurements
Authors: Starks P. J. , Zhao D. , Brown M. A.
Published: May 2008

Remote sensing of nitrogen (N) concentration and in vitro dry matter digestibility (IVDMD) in herbage can help livestock managers make timely decisions for adjusting stocking rate and managing pastures during the grazing season. Traditional laboratory analyses of N and IVDMD are time‐consuming and costly. Non‐destructive measurements of canopy hyperspectral reflectance of pasture may provide a rapid and inexpensive means of estimating these measures of nutritive value. Using a portable spectroradiometer, canopy reflectance was measured in eight warm‐season grass pastures in the USA in June and July in 2002 and 2003 to develop and validate algorithms for estimating N concentration and IVDMD of herbage. Nitrogen concentration of herbage was linearly correlated (r = 0·82; P < 0·001) with a ratio of reflectance in the 705‐ and 1685‐nm wavebands (R705/R1685) and IVDMD was correlated with R705/R535 (r = 0·74; P < 0·001). Compared with simple linear regressions of N concentration and IVDMD in herbage with two‐waveband reflectance ratios, multiple regression, using maximum r2 improvement, band‐depth analysis with step‐wise regression, and partial least‐squares regression enhanced the correlation between N concentration and IVDMD of herbage and canopy reflectance values (0·81 ≤ |r| ≤ 0·90; P < 0·001). Validation of the prediction equations indicated that multiple regression only slightly improved accuracy of a model for predicting N concentration and IVDMD of herbage compared with simple linear regression of reflectance ratios. Results suggest that the N concentration and IVDMD of herbage of warm‐season grass pastures can be rapidly and non‐destructively estimated during the grazing season using canopy reflectance in a few narrow wavebands.
Effect of temperature regime on germination of seed of perennial ryegrass (Lolium perenne)
Authors: Shen J. B. , Xu L. Y. , Jin X. Q. , Chen J. H. , Lu H. F.
Published: May 2008

Perennial ryegrass (Lolium perenne L.) is one of the most valuable temperate pasture grasses in the world. Understanding seed germination in response to temperature can help determine its optimal seeding times. Germination tests for two cultivars of perennial ryegrass (cv. ‘Turfstar’ and cv. ‘Transtar’) were conducted by applying thirty‐six constant and alternating temperature regimes, ranging from 5 to 40°C (16 h night/8 h day). Responses in germination rate to these temperature regimes were then used to construct a quadratic response surface, giving estimated germination rates with confidence intervals at P ≤ 0·05 for both cultivars. Optimum germination rate occurred over a range of regimes: 15/25, 20/25, 20/30 and 25/30°C. Furthermore, a wide range in diurnal alternating temperatures resulted in maximum seed germination rate for cv. ‘Transtar’, while no constant temperature regime supported maximum germination rate for cv. ‘Turfstar’. A temperature‐dependent germination rate function for perennial ryegrass was developed which could be used in the future to predict location‐specific optimum seeding times when national or regional monthly temperature data are available.
Leptin and varicocele‐related spermatogenesis dysfunction: animal experiment and clinical study
Authors: Chen Bin , Guo Jian‐Hua , Lu Yong‐Ning , Ying Xiao‐Lu , Hu Kai , Xiang Zu‐Qiong , Wang Yi‐Xin , Chen Pei , Huang Yi‐Ran
Published: May 2008

The objective of this study was to explore the relationships between varicocele‐related spermatogenesis dysfunction and the expression of leptin and leptin receptors. In rats with experimental varicocele, the function of spermatogenesis, the expression of leptin and leptin receptors in testes were analysed; and in patients with varicocele‐related male infertility, serum and seminal plasma levels of leptin, gonadal hormones and semen parameters were evaluated. In the testes of rats, leptin was expressed in seminiferous tubules and intersitium, leptin receptor was predominantly expressed in interstitium. The expression of leptin and its receptor in the testis of rats was not related to the weight of rat, but was inversely related to the weight of testis (r = −0.408, p = 0.009 and r = −0.433, p = 0.005, respectively), the Johnsen scores (r = −0.916, p = 0.000 and r = −0.863, p = 0.000, respectively), the seminiferous tubules diameter (r = −0.853, p = 0.000 and r = −0.870, p = 0.000, respectively) and the thickness of seminiferous epithelium (r = −0.929, p = 0.000 and r = −0.948, p = 0.000, respectively). In varicocele patients (N = 40), the sperm concentration and motility were significantly lower (p = 0.000) than those in the control group (N = 25), and the leptin level in seminal plasma was significantly higher (p = 0.000) than that in the control group. The leptin in serum and seminal plasma was positively related (r = 0.223, p = 0.002). The seminal plasma leptin level was inversely related to sperm concentration (r = −0.632, p = 0.000) and motility (r = −0.635, p = 0.000). There was no significant relation between serum leptin and seminal parameters and between leptin and gonadal hormone values. The dysfunction of spermatogenesis in varicocele‐related infertile male is associated with increase in leptin and leptin receptors. Leptin may have local effects on the function of testis and spermatogenesis.
A unique practice model for Nurse Practitioners in long‐term care homes
Authors: McAiney Carrie A. , Haughton Dilys , Jennings Jane , Farr Dave , Hillier Loretta , Morden Pat
Published: May 2008

Title.  A unique practice model for Nurse Practitioners in long‐term care homes

Aim.  This paper is a report of a study examining a practice model for Nurse Practitioners (NPs) working in long‐term care (LTC) homes and its impact on staff confidence, preventing hospital admission, and promoting early hospital discharge.

Background.  The recent introduction of NPs in LTC homes in Ontario, Canada, provided an opportunity to explore unique practice models. In a pilot project, two full‐time equivalent NPs provided primary care to a consortium of 22 homes serving approximately 2900 residents. The practice model was based on the specific needs of the homes and residents.

Methods.  The NPs working in this project prospectively collected data (from July 2003 until June 2004) on their clinical activities and resident outcomes. Directors of Care (n = 18) of the participating homes completed a questionnaire (March 2004) assessing the impact on prevention of hospitalization and staff confidence.

Findings.  The NPs had 2315 clinical contacts in the 1‐year period; the majority (64%) were follow‐up contacts. Many contacts were for uncomplicated medical problems or more complex but straightforward medical issues, and had positive outcomes. Hospital admission was prevented in 39–43% of cases. NPs had a positive impact on improving staff confidence, but no impact on facilitating early discharge from hospital.

Conclusion.  Practice models designed to meet the distinctive needs of LTC homes and residents can enhance quality of care, even with low NP:resident ratios. Participation of key stakeholders in the identification of care priorities and planning contributed to the success of this model.
The Management of Aggression and Violence Attitude Scale (MAVAS): a cross‐national comparative study
Authors: Duxbury Joy , Hahn Sabine , Needham Ian , Pulsford Dave
Published: May 2008

Title.  The Management of Aggression and Violence Attitude Scale (MAVAS): a cross‐national comparative study.

Aim.  This paper is a report of a study to determine the transferability of the Management of Aggression and Violence Attitude Scale to European mental health inpatient settings.

Background.  Incidents of patient aggression and violence are common in psychiatric in‐patient facilities, and nurses’ attitudes may play a part in how they are managed.

Methods.  Nursing staff from acute psychiatric in‐patient units in Switzerland and the United Kingdom completed the Management of Aggression and Violence Attitude Scale. Data were collected in the UK in 2001 and Switzerland in 2003. The Swiss sample comprised 75 respondents: 45 female, mean age 36·24, mean experience 7·35 years, 60 Registered Nurses. The United Kingdom sample was 75 respondents: 58 female, mean age 32, mean experience 5·25 years, 48 Registered Nurses. T‐tests identified differences between the groups in their responses to each Management of Aggression and Violence Attitude Scale statement.

Results.  There was 66% concordance of views between the groups. Swiss nurses were, however, more likely to regard factors internal to the patient as contributory to aggression while United Kingdom nurses perceived environmental factors to be more important. Both groups endorsed physical means of aggression management, Swiss nurses more so.

Conclusion.  There are both commonalities and differences between the attitudes of Swiss and United Kingdom nursing staff regarding patient aggression. Differences may relate to rates of aggression, variations in management approaches, training and policy. The Management of Aggression and Violence Attitude Scale is a potentially effective tool for making comparisons about perspectives on patient aggression.
The meaning of assisted feeding for people living with spinal cord injury: a phenomenological study
Authors: Martinsen Bente , Harder Ingegerd , Biering‐Sorensen Fin
Published: May 2008

Title.  The meaning of assisted feeding for people living with spinal cord injury: a phenomenological study

Aim.  This paper is a report of a study to explore the meaning of assisted feeding through the experiences of people with high cervical spinal cord injury.

Background.  Eating difficulties are known to affect a person’s self‐image and transform social lives. Little is known about the experience of assisted feeding as a permanent situation.

Method.  Sixteen people with high cervical spinal cord injury were interviewed twice within a period of 18 months in 2005–2006. The second interview was combined with observation. Transcriptions of interviews and notes from the observations were analysed using the phenomenological guidelines by Dahlberg and colleagues.

Findings.  The essence of the phenomenon assisted feeding was described as a constructed pattern based on coordinated attention between the person with high cervical spinal cord injury and the helper. The constituents of the essence were: paralysis as a condition of life, facing the altered meal, reconciling with diminished bodily anchoring, sensitive cooperation between self and helper, realization of own values around meals, balanced use of meal‐related devices and negotiating relationship with helpers.

Conclusion.  Assisted feeding should be adjusted to each individual person. Fixed procedures or routines should be avoided and assistive devices used with care. We recommend that continuity in the cooperation between the parties involved in assisted feeding is given priority, and that personal standard and social norms around meals are acknowledged.
Neoliberalism and human services: threat and innovation
Authors: Swenson S.
Published: May 2008

Background  The turn to neoliberalism in welfare policy suggests that human services need to be based on a market approach. The problem with this suggestion is that it presupposes marketing information such that service providers can market their services for identified client needs. In the field of intellectual disability (ID) services this type of information is not available.

Method  The method is a reflective analysis of the key presupposition of a market‐orientated approach to disability services, namely that service providers know who needs what. Using insights from marketing theory the paper engages in a reflective thought experiment to lay out the intricacies of this presupposition.

Results  The analysis results in an argument regarding the validation of a market‐based approach to disability services. First, this approach has its limits in view of the question of whether the specific and atypical needs of people with ID, as well as their financial position as potential consumers constitute a market. Second, the approach has limited validity both in view of the ability of people with ID to act as consumers, and of the restrictions imposed upon them by the eligibility criteria for welfare and support programmes.

Conclusions  A market‐based approach to disability services and supports can be helpful to spur innovation and further political and philosophical inquiry in human services, but the neoliberal optimism about the market as the only successful mechanism for service distribution is misplaced.
Pharmacokinetics of a single bolus intravenous, intramuscular and subcutaneous dose of disodium fosfomycin in horses
Authors: ZOZAYA D. H. , GUTIÉRREZ O. L. , OCAMPO C. L. , SUMANO L. H.
Published: May 2008

Pharmacokinetic parameters of fosfomycin were determined in horses after the administration of disodium fosfomycin at 10 mg/kg and 20 mg/kg intravenously (IV), intramuscularly (IM) and subcutaneously (SC) each. Serum concentration at time zero (CS0) was 112.21 ± 1.27 μg/mL and 201.43 ± 1.56 μg/mL for each dose level. Bioavailability after the SC administration was 84 and 86% for the 10 mg/kg and the 20 mg/kg dose respectively. Considering the documented minimum inhibitory concentration (MIC90) range of sensitive bacteria to fosfomycin, the maximum serum concentration (Cmax) obtained (56.14 ± 2.26 μg/mL with 10 mg/kg SC and 72.14 ± 3.04 μg/mL with 20 mg/kg SC) and that fosfomycin is considered a time‐dependant antimicrobial, it can be concluded that clinically effective plasma concentrations might be obtained for up to 10 h administering 20 mg/kg SC. An additional predictor of efficacy for this latter dose and route, and considering a 12 h dosing interval, could be area under the curve AUC0‐12/MIC90 ratio which in this case was calculated as 996 for the 10 mg/kg dose and 1260 for the 20 mg/kg dose if dealing with sensitive bacteria. If a more resistant strain is considered, the AUC0‐12/MIC90 ratio was calculated as 15 for the 10 mg/kg dose and 19 for the 20 mg/kg dose.
Viral kinetic of HCV genotype‐4 during pegylated interferon alpha 2a: ribavirin therapy
Authors: Derbala M. F. , El Dweik N. Z. , Al Kaabi S. R. , Al‐Marri A. D. , Pasic F. , Bener A. B. , Shebl F. M. , Amer A. M. , Butt M. T. , Yakoob R. , John A. , Al Mohanadi M. , Al Khinji M. A.
Published: May 2008

Summary.  Kinetics of hepatitis C virus (HCV) during pegylated interferon (PEG‐IFN) and early monitoring of viral decline were recently described to predict treatment outcomes and in turn reduce the course of treatment, adverse effects and cost. However, there is limited (if any) information on the viral dynamics of HCV‐4. Our aim is to follow the HCV‐RNA kinetics during PEG‐IFN alpha 2a and ribavirin therapy and the best time for predicting sustained viral response (SVR) in genotype‐4 patients. Serum HCV‐RNA levels before initial dosing (baseline level) and at 24 h, week 1, week 4, week 12, week 24, week 48 and week 72 were assessed in 84 HCV genotype‐4 patients treated weekly by PEG‐IFN alpha 2a and daily ribavirin. At the end of treatment, out of the 84 treated patients, 19 (22.6%) were non‐responders while 65 (77%) showed end‐of‐treatment response (ETR). However, 8 patients relapsed (9.5%), thus the SVR was observed in 57 patients (67.9%). Younger patients were more likely to attain SVR, where the odds of SVR increased by a factor of 0.94 for each year increase in age (95% CI: 0.90–0.99, P = 0.019). Although a significant negative correlation between stage of fibrosis and rate of viral decline at weeks 1 and 4 (P < 0.005 and 0.001, respectively) was seen, neither fibrosis stage (χ2 = 3.4882, P > 0.1) nor grade of inflammation (χ2 = 0.0057, P > 0.1) significantly predicted response to treatment. Non‐responders had no or only a limited decline at week 1 and week 4, whereas sustained virological responders had a significant decline at both week 1 and week 4. Area under the (receiver operating characteristic) curve (AUC) revealed that week 12 is better than any other time point in predicting the SVR (AUC = 0.97; 95% CI: 0.94–1.01), (sensitivity 98.3%; 95% CI: 90.7–99.9), (specificity 88.5%; 95% CI: 71.0–96.0), positive predictive value of 94.9% and negative predictive value of 95.8%. A drop of more than 1.17 log viral load at week 1 and viral clearance or decline >3 log were considered as the earliest predictors of SVR. In genotype‐4 patients, while failure to achieve an EVR at week 12 predicts non‐response, an RVR at week1 and week 4 98% guaranteed SVR. These findings further re‐enforce the value of week 12 in the course of IFN treatment. Genotype‐4 patients who show significant viral clearance (>1.17log viral load) by the first week of treatment and viral clearance >3log by week 4 are expected to show SVR and should therefore be assigned to a shorter drug regimen lasting for 24 weeks. Those unfortunate cases who do not achieve viral clearance by week 1 or week 4 should not be deprived from the treatment but rather given more time till week 12 before being classified as non‐responders.
Microsomal triglyceride transfer protein (MTP) –493G/T gene polymorphism contributes to fat liver accumulation in HCV genotype 3 infected patients
Authors: Zampino R. , Ingrosso D. , Durante‐Mangoni E. , Capasso R. , Tripodi M.‐F. , Restivo L. , Zappia V. , Ruggiero G. , Adinolfi L. E.
Published: May 2008

Summary.  (A) A reduced activity of microsomal triglyceride transfer protein (MTP), a key enzyme of assembly/secretion of lipoproteins, is related to HCV steatosis. Host genetic background may influence development of steatosis. The aim of the study was to investigate the association between MTP‐493 G/T gene polymorphism, fat liver accumulation and fibrosis progression in HCV infected patients. A total of 102 naïve patients with liver biopsy proven chronic hepatitis C were evaluated for MTP‐493 G/T gene polymorphism, HCV RNA, HCV genotype, HOMA‐IR, serum adiponectin, TNF‐α and serum lipid levels. HCV genotype 3 infected patients carrying the T allele of the MTP gene polymorphism showed higher degree of steatosis than those carrying GG genotype (3.45 ± 0.37 vs 1.30 ± 0.45, respectively; P < 0.001). MTP‘T’ allele carriers also had higher HCV RNA serum levels (P < 0.01) and hepatic fibrosis (P < 0.001). Irrespective of MTP genotype, patients with HCV genotype 3 had lower levels of cholesterol, ApoB, HDL and LDL. In HCV genotype non‐3 infected patients no parameters were associated with MTP gene polymorphism. In conclusion the presence of T allele of MTP‐493G/T gene polymorphism predisposes patients infested with HCV genotype 3 to develop higher degree of fatty liver accumulation.
A redundancy of processes that cause replication fork stalling enhances recombination at two distinct sites in yeast rDNA
Authors: Mayán‐Santos M. D. , Martínez‐Robles M. L. , Hernández P. , Schvartzman J. B. , Krimer D. B.
Published: May 2008

DNA recombination was investigated by monitoring integration at the rDNA of a circular minichromosome containing a 35S minigene and a replication fork barrier (RFB). The effects of replication fork stalling on integration were studied in wild‐type, FOB1Δ, SIR2Δ and the double mutant FOB1ΔSIR2Δ cells. The results obtained confirmed that Sir2p represses and replication fork stalling enhances integration of the minichromosome. This integration, however, only took place at two distinct sites: the RFB and the 3′ end of the 35S gene. For integration to take place at the 35S gene, replication fork stalling must occur at the 3′ end of the gene in both the minichromosome and the chromosomal repeats. Integration at the RFB, on the other hand, occurred readily in FOB1Δ cells, indicating that more than a single mechanism triggers homologous recombination at this site. Altogether, these observations strongly suggest that the main role for replication fork stalling at the rDNA locus is to promote homologous recombination rather than just to prevent head‐on collision of transcription and replication as originally thought.
Colicin E3 cleavage of 16S rRNA impairs decoding and accelerates tRNA translocation on Escherichia coli ribosomes
Authors: Lancaster Lorna E. , Savelsbergh Andreas , Kleanthous Colin , Wintermeyer Wolfgang , Rodnina Marina V.
Published: May 2008

The cytotoxin colicin E3 targets the 30S subunit of bacterial ribosomes and specifically cleaves 16S rRNA at the decoding centre, thereby inhibiting translation. Although the cleavage site is well known, it is not clear which step of translation is inhibited. We studied the effects of colicin E3 cleavage on ribosome functions by analysing individual steps of protein synthesis. We find that the cleavage affects predominantly the elongation step. The inhibitory effect of colicin E3 cleavage originates from the accumulation of sequential impaired decoding events, each of which results in low occupancy of the A site and, consequently, decreasing yield of elongating peptide. The accumulation leads to an almost complete halt of translation after reading of a few codons. The cleavage of 16S rRNA does not impair monitoring of codon–anticodon complexes or GTPase activation during elongation‐factor Tu‐dependent binding of aminoacyl‐tRNA, but decreases the stability of the codon–recognition complex and slows down aminoacyl‐tRNA accommodation in the A site. The tRNA–mRNA translocation is faster on colicin E3‐cleaved than on intact ribosomes and is less sensitive to inhibition by the antibiotic viomycin.