bluuebunny/crossref_metadata_2025 huggingface dataset:
Climate change frames debate over the extinction of megafauna in Sahul (Pleistocene Australia-New Guinea)
Authors: Wroe Stephen , Field Judith H. , Archer Michael , Grayson Donald K. , Price Gilbert J. , Louys Julien , Faith J. Tyler , Webb Gregory E. , Davidson Iain , Mooney Scott D.
Published: May 2013

Around 88 large vertebrate taxa disappeared from Sahul sometime during the Pleistocene, with the majority of losses (54 taxa) clearly taking place within the last 400,000 years. The largest was the 2.8-ton browsingDiprotodon optatum, whereas the ∼100- to 130-kg marsupial lion,Thylacoleo carnifex, the world’s most specialized mammalian carnivore, andVaranus priscus, the largest lizard known, were formidable predators. Explanations for these extinctions have centered on climatic change or human activities. Here, we review the evidence and arguments for both. Human involvement in the disappearance of some species remains possible but unproven. Mounting evidence points to the loss of most species before the peopling of Sahul (circa 50–45 ka) and a significant role for climate change in the disappearance of the continent’s megafauna.
Phosphorylation-dependent conformational changes and domain rearrangements in
Staphylococcus aureus
VraR activation
Authors: Leonard Paul G. , Golemi-Kotra Dasantila , Stock Ann M.
Published: May 2013

Staphylococcus aureus
VraR, a vancomycin-resistance-associated response regulator, activates a cell-wall–stress stimulon in response to antibiotics that inhibit cell wall formation. X-ray crystal structures of VraR in both unphosphorylated and beryllofluoride-activated states have been determined, revealing a mechanism of phosphorylation-induced dimerization that features a deep hydrophobic pocket at the center of the receiver domain interface. Unphosphorylated VraR exists in a closed conformation that inhibits dimer formation. Phosphorylation at the active site promotes conformational changes that are propagated throughout the receiver domain, promoting the opening of a hydrophobic pocket that is essential for homodimer formation and enhanced DNA-binding activity. This prominent feature in the VraR dimer can potentially be exploited for the development of novel therapeutics to counteract antibiotic resistance in this important pathogen.
Farnesylation of lamin B1 is important for retention of nuclear chromatin during neuronal migration
Authors: Jung Hea-Jin , Nobumori Chika , Goulbourne Chris N. , Tu Yiping , Lee John M. , Tatar Angelica , Wu Daniel , Yoshinaga Yuko , de Jong Pieter J. , Coffinier Catherine , Fong Loren G. , Young Stephen G.
Published: May 2013

Significance

Both lamin B1 and lamin B2 have farnesyl lipid anchors, but the importance of this lipid modification has been unclear. We addressed that issue with knock-in mouse models. Mice expressing nonfarnesylated lamin B2 developed normally and were healthy. In contrast, mice expressing nonfarnesylated lamin B1 exhibited a severe neurodevelopmental abnormality accompanied by a striking defect in the cell nucleus. During the migration of neurons, the nuclear lamina was pulled free of the chromatin. Thus, farnesylation of lamin B1—but not lamin B2—is crucial for neuronal migration in the brain and for the retention of chromatin within the nuclear lamina.
Control of slippage with tunable bubble mattresses
Authors: Karatay Elif , Haase A. Sander , Visser Claas Willem , Sun Chao , Lohse Detlef , Tsai Peichun Amy , Lammertink Rob G. H.
Published: May 2013

Tailoring the hydrodynamic boundary condition is essential for both applied and fundamental aspects of drag reduction. Hydrodynamic friction on superhydrophobic substrates providing gas–liquid interfaces can potentially be optimized by controlling the interface geometry. Therefore, establishing stable and optimal interfaces is crucial but rather challenging. Here we present unique superhydrophobic microfluidic devices that allow the presence of stable and controllable microbubbles at the boundary of microchannels. We experimentally and numerically examine the effect of microbubble geometry on the slippage at high resolution. The effective slip length is obtained for a wide range of protrusion angles,
θ
, of the microbubbles into the flow, using a microparticle image velocimetry technique. Our numerical results reveal a maximum effective slip length, corresponding to a 23% drag reduction at an optimal
θ
≈ 10°. In agreement with the simulation results, our measurements correspond to up to 21% drag reduction when
θ
is in the range of −2° to 12°. The experimental and numerical results reveal a decrease in slip length with increasing protrusion angles when
θ
≳ 10°. Such microfluidic devices with tunable slippage are essential for the amplified interfacial transport of fluids and particles.
Study of the fluoro- and chlorodimethylbutyl cations
Authors: Olah George A. , Prakash G. K. Surya , Rasul Golam
Published: May 2013

A comparative study of the 2,3-dimethyl-3-fluoro-2-butyl cation and its chloro analog was carried out by the ab initio/GIAO-CCSD(T) (gauge invariant atomic orbital-coupled cluster with single, double, and perturbative triple excitation) method. The structures and
13
C NMR chemical shifts of the cations were calculated at the GIAO-CCSD(T)/tzp/dz//MP2/cc-pVTZ level. Bridged fluoronium ion 1, carbenium ion 2, and fluorocarbenium ion 3 were found to be minima on the potential energy surface. Bridged fluoronium ion 1, although a minimum on the potential energy surface, is 12.8 kcal/mol less stable than the open chain fluorobutyl cation 3. In contrast to the fluorinated ion, bridged chloronium ion 5 was found to be the lowest energy minimum being 10.6 kcal/mol more stable than ion 6 and 7.4 kcal/mol more stable than ion 7.
Structural snapshots reveal distinct mechanisms of procaspase-3 and -7 activation
Authors: Thomsen Nathan D. , Koerber James T. , Wells James A.
Published: May 2013

Procaspase-3 (P3) and procaspase-7 (P7) are activated through proteolytic maturation to form caspase-3 (C3) and caspase-7 (C7), respectively, which serve overlapping but nonredundant roles as the executioners of apoptosis in humans. However, it is unclear if differences in P3 and P7 maturation mechanisms underlie their unique biological functions, as the structure of P3 remains unknown. Here, we report structures of P3 in a catalytically inactive conformation, structures of P3 and P7 bound to covalent peptide inhibitors that reveal the active conformation of the zymogens, and the structure of a partially matured C7:P7 heterodimer. Along with a biochemical analysis, we show that P3 is catalytically inactive and matures through a symmetric all-or-nothing process. In contrast, P7 contains latent catalytic activity and matures through an asymmetric and tiered mechanism, suggesting a lower threshold for activation. Finally, we use our structures to design a selection strategy for conformation specific antibody fragments that stimulate procaspase activity, showing that executioner procaspase conformational equilibrium can be rationally modulated. Our studies provide a structural framework that may help to explain the unique roles of these important proapoptotic enzymes, and suggest general strategies for the discovery of proenzyme activators.
Combined effect of a peptide–morpholino oligonucleotide conjugate and a cell-penetrating peptide as an antibiotic
Authors: Wesolowski Donna , Alonso Dulce , Altman Sidney
Published: May 2013

A cell-penetrating peptide (CPP)–morpholino oligonucleotide (MO) conjugate (PMO) that has an antibiotic effect in culture had some contaminating CPPs in earlier preparations. The mixed conjugate had gene-specific and gene-nonspecific effects. An improved purification procedure separates the PMO from the free CPP and MO. The gene-specific effects are a result of the PMO, and the nonspecific effects are a result of the unlinked, unreacted CPP. The PMO and the CPP can be mixed together, as has been shown previously in earlier experiments, and have a combined effect as an antibiotic. Kinetic analysis of these effects confirm this observation. The effect of the CPP is bacteriostatic. The effect of the PMO appears to be bacteriocidal. An assay for mutations that would alter the ability of these agents to affect bacterial viability is negative.
The asymmetric segregation of damaged proteins is stem cell–type dependent
Authors: Bufalino Mary Rose , DeVeale Brian , van der Kooy Derek
Published: May 2013

Asymmetric segregation of damaged proteins (DPs) during mitosis has been linked in yeast and bacteria to the protection of one cell from aging. Recent evidence suggests that stem cells may use a similar mechanism; however, to date there is no in vivo evidence demonstrating this effect in healthy adult stem cells. We report that stem cells in larval (neuroblast) and adult (female germline and intestinal stem cell) Drosophila melanogaster asymmetrically segregate DPs, such as proteins with the difficult-to-degrade and age-associated 2,4-hydroxynonenal (HNE) modification. Surprisingly, of the cells analyzed only the intestinal stem cell protects itself by segregating HNE to differentiating progeny, whereas the neuroblast and germline stem cells retain HNE during division. This led us to suggest that chronological life span, and not cell type, determines the amount of DPs a cell receives during division. Furthermore, we reveal a role for both niche-dependent and -independent mechanisms of asymmetric DP division.
Defective nuclear import of Tpr in Progeria reflects the Ran sensitivity of large cargo transport
Authors: Snow Chelsi J. , Dar Ashraf , Dutta Anindya , Kehlenbach Ralph H. , Paschal Bryce M.
Published: May 2013

The RanGTPase acts as a master regulator of nucleocytoplasmic transport by controlling assembly and disassembly of nuclear transport complexes. RanGTP is required in the nucleus to release nuclear localization signal (NLS)–containing cargo from import receptors, and, under steady-state conditions, Ran is highly concentrated in the nucleus. We previously showed the nuclear/cytoplasmic Ran distribution is disrupted in Hutchinson-Gilford Progeria syndrome (HGPS) fibroblasts that express the Progerin form of lamin A, causing a major defect in nuclear import of the protein, translocated promoter region (Tpr). In this paper, we show that Tpr import was mediated by the most abundant import receptor, KPNA2, which binds the bipartite NLS in Tpr with nanomolar affinity. Analyses including NLS swapping revealed Progerin did not cause global inhibition of nuclear import. Rather, Progerin inhibited Tpr import because transport of large protein cargoes was sensitive to changes in the Ran nuclear/cytoplasmic distribution that occurred in HGPS. We propose that defective import of large protein complexes with important roles in nuclear function may contribute to disease-associated phenotypes in Progeria.
Glucocorticoids alleviate intestinal ER stress by enhancing protein folding and degradation of misfolded proteins
Authors: Das Indrajit , Png Chin Wen , Oancea Iulia , Hasnain Sumaira Z. , Lourie Rohan , Proctor Martina , Eri Rajaraman D. , Sheng Yong , Crane Denis I. , Florin Timothy H. , McGuckin Michael A.
Published: May 2013

Endoplasmic reticulum (ER) stress in intestinal secretory cells has been linked with colitis in mice and inflammatory bowel disease (IBD). Endogenous intestinal glucocorticoids are important for homeostasis and glucocorticoid drugs are efficacious in IBD. In Winnie mice with intestinal ER stress caused by misfolding of the Muc2 mucin, the glucocorticoid dexamethasone (DEX) suppressed ER stress and activation of the unfolded protein response (UPR), substantially restoring goblet cell Muc2 production. In mice lacking inflammation, a glucocorticoid receptor antagonist increased ER stress, and DEX suppressed ER stress induced by the N-glycosylation inhibitor, tunicamycin (Tm). In cultured human intestinal secretory cells, in a glucocorticoid receptor-dependent manner, DEX suppressed ER stress and UPR activation induced by blocking N-glycosylation, reducing ER Ca2+ or depleting glucose. DEX up-regulated genes encoding chaperones and elements of ER-associated degradation (ERAD), including EDEM1. Silencing EDEM1 partially inhibited DEX’s suppression of misfolding-induced ER stress, showing that DEX enhances ERAD. DEX inhibited Tm-induced MUC2 precursor accumulation, promoted production of mature mucin, and restored ER exit and secretion of Winnie mutant recombinant Muc2 domains, consistent with enhanced protein folding. In IBD, glucocorticoids are likely to ameliorate ER stress by promoting correct folding of secreted proteins and enhancing removal of misfolded proteins from the ER.
TNF receptor associated factor 3 plays a key role in development and function of invariant natural killer T cells
Authors: Yi Zuoan , Stunz Laura L. , Bishop Gail A.
Published: May 2013

TCR signaling is a prerequisite for early stage development of invariant natural killer T (iNKT) cells, whereas IL-15 signaling is required for expansion and maturation at later stages. In this study, we show that TNF receptor associated factor 3 (TRAF3) plays a critical role in the transition between these two distinct signaling pathways and developmental stages. TRAF3-deficient iNKT cells in CD4CreTRAF3flox/flox (T-TRAF3−/−) mice exhibit defective up-regulation of T-bet and CD122, two critical molecules for IL-15 signaling, and as a consequence, IL-15–mediated iNKT cell proliferation and survival are impaired. Consistently, development of iNKT cells in T-TRAF3−/− mice shows a major defect at developmental stages 2 and 3, but not stages 0 and 1. We further demonstrated that defective T-bet up-regulation occurring during the stage 1 to stage 2 transition results from reduced TCR signaling in TRAF3−/− iNKT cells. In addition, mature TRAF3−/− iNKT cells displayed defective cytokine responses upon TCR stimulation. Collectively, our results reveal that by modulating the relative strength of TCR signaling, TRAF3 is an important regulator of iNKT cell development and functions.
IL-2–dependent adaptive control of NK cell homeostasis
Authors: Gasteiger Georg , Hemmers Saskia , Bos Paula D. , Sun Joseph C. , Rudensky Alexander Y.
Published: May 2013

Activation and expansion of T and B lymphocytes and myeloid cells are controlled by Foxp3+ regulatory T cells (T reg cells), and their deficiency results in a fatal lympho- and myeloproliferative syndrome. A role for T reg cells in the homeostasis of innate lymphocyte lineages remained unknown. Here, we report that T reg cells restrained the expansion of immature CD127+ NK cells, which had the unique ability to up-regulate the IL2Rα (CD25) in response to the proinflammatory cytokine IL-12. In addition, we observed the preferential accumulation of CD127+ NK cells in mice bearing progressing tumors or suffering from chronic viral infection. CD127+ NK cells expanded in an IL-2–dependent manner upon T reg cell depletion and were able to give rise to mature NK cells, indicating that the latter can develop through a CD25+ intermediate stage. Thus, T reg cells restrain the IL-2–dependent CD4+ T cell help for CD127+ immature NK cells. These findings highlight the adaptive control of innate lymphocyte homeostasis.
Preferences of heart failure patients in daily clinical practice: quality of life or longevity?
Authors: Kraai Imke H. , Vermeulen Karin M. , Luttik Marie Louise A. , Hoekstra Tialda , Jaarsma Tiny , Hillege Hans L.
Published: May 2013

Aims

Knowledge of patient preferences is vital for delivering optimal healthcare. This study uses utility measurement to assess the preferences of heart failure (HF) patients regarding quality of life or longevity. The utility approach represents the perspective of a patient; facilitates the combination of mortality, morbidity, and treatment regimen into a single score; and makes it possible to compare the effects of different interventions in healthcare.

Methods and results

Patient preferences of 100 patients with HF were assessed in interviews using the time trade‐off (TTO) approach. Health‐related quality of life (HR‐QoL) was assessed with the EQ‐5D and the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Patients' own estimation of life expectancy was assessed with a visual analogue scale (VAS). Of the 100 patients (mean age 70 ± 9 years; 71% male), 61% attach more weight to quality of life over longevity; while 9% and 14% were willing to trade 6 and 12 months, respectively, for perfect health and attach more weight to quality of life. Patients willing to trade time had a significantly higher level of NT‐proBNP and reported significantly more dyspnoea during exertion. Predictors of willingness to trade time were higher NT‐proBNP and lower EQ VAS.

Conclusion

The majority of HF patients attach more weight to quality of life over longevity. There was no difference between both groups with respect to life expectancy described by the patients. These insights enable open and personalized discussions of patients' preferences in treatment and care decisions, and could guide the future development of more patient‐centred care.
In Vitro Starch Digestibility and Expected Glycemic Index of Kodo Millet (Paspalum scrobiculatum) as Affected by Starch–Protein–Lipid Interactions
Authors: Annor George Amponsah , Marcone Massimo , Bertoft Eric , Seetharaman Koushik
Published: May 2013

The effect of starch–protein–lipid interaction on the in vitro starch digestibility and expected glycemic index (eGI) of kodo millet flour (MF) was investigated. Debranned MF and the flour with lipid removed, protein removed, or both lipid and protein removed (MF‐L‐P) were subjected to digestion assays. The in vitro starch digestibility and eGI of the millet samples and millet starch were compared with rice or wheat flour. Rapidly digestible starch, slowly digestible starch, and resistant starch (RS) of the samples were also calculated. Protease treatment and defatting resulted in significant reduction (P < 0.05) in protein and lipid contents of samples. Significant increases in the in vitro starch digestibility and eGI of samples were observed after removal of protein, lipid, or both. The effect of lipid removal on in vitro starch digestibility of kodo millet was found to be more significant, compared with when proteins were removed. The eGI increased from 49.4 for cooked MF to 62.5 for MF‐L‐P. The eGI of cooked kodo millet starch was significantly lower than that of cooked rice flour. The RS (1.61%) of cooked rice was the least among the samples. The in vitro starch digestibility and eGI of rice were significantly higher than those of MF. Processes applied to kodo millet, such as decortication, that result in the removal of proteins, lipids, or both (especially lipids) would result in an increase in its in vitro starch digestibility and eGI. We therefore advocate for the development of acceptable products from whole millets to maintain its hypoglycemic property.
RB goes mitochondrial
Authors: Attardi Laura D. , Sage Julien
Published: May 2013

The retinoblastoma tumor suppressor RB is well known for its capacity to restrict cell cycle progression at the G1/S transition of the cell cycle by controlling the transcription of cell cycle genes. In this issue of Genes & Development, Hilgendorf and colleagues (pp. 1003–1015) have identified a novel tumor suppressor function for RB independent of its role as a transcriptional regulator, in which RB directly activates the apoptosis regulator Bax at the mitochondria to promote cell death.
Identification of cellular factors required for the budding of koala retrovirus
Authors: Shimode Sayumi , Nakaoka Rie , Hoshino Shigeki , Abe Masumi , Shogen Hiroko , Yasuda Jiro , Miyazawa Takayuki
Published: May 2013

Koala retrovirus (KoRV) is a unique gammaretrovirus that is currently endogenizing into its host and considered to be associated with leukemia, lymphoma and immunosuppression in koalas (Phascolactos cinereus). In this study, it was demonstrated that WWP2 or WWP2‐like E3 ubiquitin ligases possessing the WW domain closely related to WWP2 and Vps4A/B are involved in KoRV budding. These data suggest that KoRV Gag recruits the cellular endosomal sorting complex required for transport machinery through interaction of the PPPY L‐domain with the WW domain(s) of WWP2 and that progeny virions are released from cells by utilizing the multivesicular body sorting pathway.
Effects of ceftriaxone‐induced intestinal dysbacteriosis on dendritic cells of small intestine in mice
Authors: Li Ming , Li Weihua , Wen Shu , Liu Yinhui , Tang Li
Published: May 2013

Intestinal microflora plays a pivotal role in the development of the innate immune system and is essential in shaping adaptive immunity. Dysbacteriosis of intestinal microflora induces altered immune responses and results in disease susceptibility. Dendritic cells (DCs), the professional antigen‐presenting cells, have gained increasing attention because they connect innate and adaptive immunity. They generate both immunity in response to stimulation by pathogenic bacteria and immune tolerance in the presence of commensal bacteria. However, few studies have examined the effects of intestinal dysbacteriosis on DCs. In this study, changes of DCs in the small intestine of mice under the condition of dysbacteriosis induced by ceftriaxone sodium were investigated. It was found that intragastric administration of ceftriaxone sodium caused severe dysteriosis in mice. Compared with controls, numbers of DCs in mice with dysbacteriosis increased significantly (P = 0.0001). However, the maturity and antigen‐presenting ability of DCs were greatly reduced. In addition, there was a significant difference in secretion of IL‐10 and IL‐12 between DCs from mice with dysbacteriosis and controls. To conclude, ceftriaxone‐induced intestinal dysbacteriosis strongly affected the numbers and functions of DCs. The present data suggest that intestinal microflora plays an important role in inducing and maintaining the functions of DCs and thus is essential for the connection between innate and adaptive immune responses.
Are Cape gannets dependent upon fishery waste? A multi‐scale analysis using seabird GPS‐tracking, hydro‐acoustic surveys of pelagic fish and vessel monitoring systems
Authors: Tew Kai Emilie , Benhamou Simon , van der Lingen Carl D. , Coetzee Janet C. , Pichegru Lorien , Ryan Peter G. , Grémillet David
Published: May 2013

Climate change and fishing impact marine ecosystems, potentially modifying the availability of small pelagic fish to marine top predators. Some seabirds that primarily rely upon these resources have switched to feeding on fishery waste. It has therefore been argued that seabirds might become dependent upon this artificial resource.

To test this hypothesis, we studied the foraging behaviour of Cape gannets Morus capensis breeding off the coast of South Africa using high‐resolution Global Positioning System‐tracking in relation to the availability of pelagic fish assessed by acoustic at‐sea surveys, and fishing effort by the two main south African fisheries (purse seiners that compete with seabirds for pelagic fish, and demersal trawlers that process fish at sea and discharge fish waste) tracked with vessel monitoring systems. Conjoint seabird, fish and fisheries information were analysed at mesoscale (c. 100 km) and sub‐mesoscale (c. 10 km) in years of high (2002), medium (2009) and low (2005) pelagic fish biomass within gannets' foraging range.

We found substantial inter‐annual variability in spatial use by breeding gannets, which was driven primarily by pelagic fish availability. At the mesoscale, birds and purse seiners exploited similar marine areas, but no fine‐scale dependence of birds on purse seiners was detected. Crucially, fine‐scale dependence of gannets upon trawlers producing fishery waste was only detected in 2005, when pelagic fish biomass was lowest, indicating a direct effect of trawlers on gannet foraging behaviour in the absence of natural prey.

Further overlap analyses of gannet and trawler foraging areas during 2002–2010 confirmed that breeding birds only seek trawlers when pelagic fish availability is low, strongly suggesting reversible seabird dependency upon fishery waste.

Synthesis and applications. Our study demonstrates that seabirds such as Cape gannets depend on fishery waste when their natural prey is scarce, but revert to feeding on natural resources whenever available, showing highly flexible foraging behaviour. These results have important implications in the context of the anticipated legislation banning at‐sea disposal of fishery waste in different regions, including European seas, highlighting the necessity to concomitantly promote sustainable fishing allowing the restoration of pelagic fish stocks.
Functional differentiation between the inner and outer leaves in a mechanical support by a pseudostem of Veratrum album subsp. oxysepalum
Authors: Gu Lingshuang , Konno Yasuo , Yamamoto Shinro
Published: May 2013

The pseudostem of Veratrum album subsp. oxysepalum consists of radical leaves, which have tubular and concentrically aggregated petioles. We examined a hypothesis that the major role of the inner leaves is to raise the leaf blades higher for increased photosynthesis, while that of the outer leaves is to mechanically support the inner leaves at the expense of displaying their leaf blades. The removal of outer leaves resulted in the collapse of the remaining inner leaves, showing outer leaves provide important support for inner leaves. The estimation of mechanical properties for the constituting leaves revealed that inner leaves possess greater mass of leaf blades for their capacity of mechanical support them compared to outer leaves. These results uphold the hypothesis that the primary role of inner leaves is to display leaf blades for photosynthesis, while that for outer leaves is to mechanically support the less stable inner leaves.
Overlapping and Evolving European Discourses on Market Liberalization
Authors: Morin Jean-Frédéric , Carta Caterina
Published: May 2013

Research Highlights and Abstract

This introduction to the special section on European liberal discourses

Presents key assumptions discussed in the collection of articles, such as liberalism as a discourse and the conceptualization of discourses as networks. Offers an original typology of liberal discourses regarding State intervention. Introduces two models linking discursive interactions to discursive change, analogous to the operational code approach and to schema theory in cognitive science. Presents original data on DG Trade discourse, to illustrate simultaneous change and continuity.

This introduction to the special section on European liberal discourses discusses three themes covered by all contributions: (i) the co-existence of several market liberal discourses in the European public sphere; (ii) interactions among these various discourses; (iii) and discursive changes resulting from these interactions.
Cost and resource implications with serum angiogenic factor estimation in the triage of pre‐eclampsia
Authors: Schnettler WT , Dukhovny D , Wenger J , Salahuddin S , Ralston SJ , Rana S
Published: May 2013

Objectives

To analyse the economic and resource implications of using plasma soluble fms‐like tyrosine kinase‐1 s(Flt1) and placenta growth factor (PlGF) measurements in pre‐eclampsia evaluation and management.

Design

Retrospective cost analysis of our prospective cohort study.

Setting

Boston, Massachusetts (USA).

Population

Women (n = 176) presenting to the hospital at <34 weeks of gestation for evaluation of possible pre‐eclampsia during 2009–10. Cases without complete cost or outcome data (n = 9) and re‐enrolments (n = 18) were excluded.

Methods

Modelled comparisons between the standard approach (combination of blood pressure, urinary protein excretion, alanine aminotransferase and platelet counts) and a novel approach (ratio of plasma sFlt1 and PlGF) using actual hospital data converted to 2012 US dollars in accordance with the Centers for Medicare and Medicaid Services.

Main outcome measures

Direct 2‐week costs and resource use by groups having true or false positive and negative test results for adverse outcomes according to approach.

Results

The improved specificity of the novel approach decreased the proportion of women falsely labelled as test‐positive from 42.3% (34.4–50.2%) to 4.0% (0.85–7.15%) and increased the proportion correctly labelled as test‐negative from 23.5% (16.7–30.3%) to 61.7% (53.9–69.5%). This could potentially reduce average per‐patient costs by $1215. Substantial quantities of resources [47.2% (35.7–58.7%) of antenatal admissions and 72.5% (68.0–77.0%) of tests for fetal wellbeing] were unnecessarily used for women who were truly negative. A proportion of iatrogenic preterm deliveries among women with negative results was potentially avoidable representing further cost and resource savings.

Conclusions

Clinical use of the plasma sFlt1 and PlGF ratio improves risk stratification among women presenting for pre‐eclampsia evaluation and has the potential to reduce costs and resource use.
Measurement invariance of DSM‐IV alcohol, marijuana and cocaine dependence between community‐sampled and clinically overselected studies
Authors: Derringer Jaime , Krueger Robert F. , Dick Danielle M. , Agrawal Arpana , Bucholz Kathleen K. , Foroud Tatiana , Grucza Richard A. , Hesselbrock Michie N. , Hesselbrock Victor , Kramer John , Nurnberger John I. , Schuckit Marc , Bierut Laura J. , Iacono William G. , McGue Matt
Published: May 2013

Aims

To examine whether DSM‐IV symptoms of substance dependence are psychometrically equivalent between existing community‐sampled and clinically overselected studies.

Participants

A total of 2476 adult twins born in Minnesota and 4121 unrelated adult participants from a case–control study of alcohol dependence.

Measurements

Life‐time DSM‐IV alcohol, marijuana and cocaine dependence symptoms and ever use of each substance.

Design

We fitted a hierarchical model to the data, in which ever use and dependence symptoms for each substance were indicators of alcohol, marijuana or cocaine dependence which were, in turn, indicators of a multi‐substance dependence factor. We then tested the model for measurement invariance across participant groups, defined by study source and participant sex.

Findings

The hierarchical model fitted well among males and females within each sample [comparative fit index (CFI) > 0.96, Tucker–Lewis index (TLI) > 0.95 and root mean square error of approximation (RMSEA) < 0.04 for all], and a multi‐group model demonstrated that model parameters were equivalent across sample‐ and sex‐defined groups (ΔCFI = 0.002 between constrained and unconstrained models). Differences between groups in symptom endorsement rates could be expressed solely as mean differences in the multi‐substance dependence factor.

Conclusions

Life‐time substance dependence symptoms fitted a dimensional model well. Although clinically overselected participants endorsed more dependence symptoms, on average, than community‐sampled participants, the pattern of symptom endorsement was similar across groups. From a measurement perspective, DSM‐IV criteria are equally appropriate for describing substance dependence across different sampling methods.
A novel c.‐274C>G polymorphism in bovine SIRT1 gene contributes to diminished promoter activity and is associated with increased body size
Authors: Li Ming‐xun , Sun Xiao‐mei , Zhang Liang‐zhi , Wang Jing , Huang Yong‐zhen , Sun Yu‐jia , Hu Shen‐rong , Lan Xian‐yong , Lei Chu‐zhao , Chen Hong
Published: May 2013

SIRT1, a mammalian homologue for yeast silent information regulator 2 (SIR2), is a NAD+‐dependent deacetylase that belongs to the class III histone deacetylases. It plays an important role in diverse cellular processes, including stress resistance, mitochondrial function, suppression of inflammation and DNA repair. In this study, we screened and identified a novel polymorphism (c.‐274C>G) in the SIRT1 promoter region. In silico prediction reveals that this SNP is in the core of cell cycle‐dependent element (CDE)‐binding motif. Interestingly, the G allele abolished a CDE‐binding site, which suggested its functional significance. In the luciferase assay system, we found that the G allele‐containing construct displayed a strikingly lower promoter activity compared with the C allele, which may downregulate SIRT1 expression levels. Additionally, we observed a significant association between the c.‐274C>G polymorphism and growth traits in Nanyang cattle, suggesting that anomalous transcription factor‐based repression of SIRT1 may increase bovine fat mass and body size.
Confirmation and fine‐mapping of clinical mastitis and somatic cell score QTL in Nordic Holstein cattle
Authors: Sahana G. , Guldbrandtsen B. , Thomsen B. , Lund M. S.
Published: May 2013

A genome‐wide association study of 2098 progeny‐tested Nordic Holstein bulls genotyped for 36 387 SNPs on 29 autosomes was conducted to confirm and fine‐map quantitative trait loci (QTL) for mastitis traits identified earlier using linkage analysis with sparse microsatellite markers in the same population. We used linear mixed model analysis where a polygenic genetic effect was fitted as a random effect and single SNPs were successively included as fixed effects in the model. We detected 143 SNP‐by‐trait significant associations (P < 0.0001) on 20 chromosomes affecting mastitis‐related traits. Among them, 21 SNP‐by‐trait combinations exceeded the genome‐wide significant threshold. For 12 chromosomes, both the present association study and the previous linkage study detected QTL, and of these, six were in the same chromosomal locations. Strong associations of SNPs with mastitis traits were observed on bovine autosomes 6, 13, 14 and 20. Possible candidate genes for these QTL were identified. Identification of SNPs in linkage disequilibrium with QTL will enable marker‐based selection for mastitis resistance. The candidate genes identified should be further studied to detect candidate polymorphisms underlying these QTL.
The Influence of Restricted Feeding on Glucagon‐Like Peptide‐1 (GLP‐1)‐Containing Cells in the Chicken Small Intestine
Authors: Monir M. M. , Hiramatsu K. , Yamasaki A. , Nishimura K. , Watanabe T.
Published: May 2013

The influence of restricted feeding on the distribution of glucagon‐like peptide‐1 (GLP‐1)‐containing endocrine cells in the chicken small intestine was investigated using immunohistochemical and morphometrical techniques. This study demonstrated that the restricted feeding had an influence on the activity of GLP‐1‐immunoreactive cells in the chicken small intestine. There were differences in the localization and the frequency of occurrence of GLP‐1‐immunoreactive cells in the small intestine between control and restricted groups, especially 25% feed supply group provided with 25% of the intake during the adapting period. GLP‐1‐immunoreactive cells in the control chickens were mainly located in epithelium from crypts to the lower part of intestinal villi. Those in restricted groups, however, tended to be located from crypts to the middle part of intestinal villi. The frequency of occurrence of GLP‐1‐immunoreactive cells was lowest in the control group, medium in 50% feed supply group and highest in 25% feed supply group at each intestinal region examined in this study, that is, increased with the advancement of restricting the amount of feed supply. These data show that the quantity of food intake is one of signals that have an influence on the secretion of GLP‐1 from L cells in the chicken small intestine.
Early vitreoretinal surgery on vascularly active stage 4 retinopathy of prematurity through the preoperative intravitreal bevacizumab injection
Authors: Xu Yu , Zhang Qi , Kang Xiaoli , Zhu Ying , Li Jiakai , Chen Yiye , Zhao Peiquan
Published: May 2013

Purpose:  To evaluate the effect of early vitreoretinal surgery on vascularly active stage 4 ROP through the preoperative use of intravitreal bevacizumab.

Methods:  This was a retrospective study. Eighteen patients with vascularly active stage 4 ROP who underwent primary vitrectomy from April 2007 to March 2010 were enrolled. Twelve eyes from eight patients received one‐time intravitreal injection of 0.625 mg bevacizumab 7 days prior to vitrectomy (bevacizumab group), and 11 eyes from 10 patients underwent the surgical procedure without bevacizumab (control group). Demographical information of all patients was recorded. The patients were followed up for 12–36 months after the surgery. The postmenstrual age at vitrectomy, surgical procedure, anatomical and visual outcome, adverse effects and surgical complications were compared.

Results:  There was no statistically significant difference between the two groups in gender, birthweight and gestational age. The bevacizumab group showed remarkable regression of vascular activity after the injection. The mean postmenstrual age at the time of vitrectomy was significantly earlier in the bevacizumab group (40 versus 47 weeks, p = 0.002) compared with the controls. The mean surgery time was shorter in the bevacizumab group (74.81 versus 101.70 min, bevacizumab group versus control, p = 0.002). At the final follow‐up, all patients in the bevacizumab group achieved anatomical retinal attachment, compared with 70% in the control group. Eighty‐eight per cent patients in the bevacizumab group obtained pattern vision, while it was 30% in the control group (p = 0.015).

Conclusion:  Intravitreal bevacizumab administrated prior to vitrectomy effectively reduced active neovascularization in vascularly active stage 4 ROP patients, thus advancing the timing of vitrectomy and facilitating pars plicata vitrectomy (PPV).
Attitudes towards People with Disabilities – what do people with intellectual disabilities have to say?
Authors: Corr McEvoy Sandra , Keenan Emer
Published: May 2013

Accessible summary

This research aimed to find out how people with intellectual disabilities are treated by the public, from the viewpoint of people with intellectual disabilities.

A total of seven focus groups were used to collect stories from 41 adults with intellectual disabilities attending one agency in Dublin.

The stories were about how they have been treated in everyday life.

The findings show that some people have been treated very well, but many other people have not been treated well.

Attitudes towards people with intellectual disabilities have traditionally been very negative, resulting in people with intellectual disabilities being treated badly by other. This claim was explored by conducting focus groups with adults who have an intellectual disability to find out about their everyday experiences in different places and using different services. Participants reported being treated well by some people and in some places, but being treated less favourably by other people and in other places. Being treated well happened in their home, in college, in work and in their services. People were treated less well when they were out and about, using public transport, in school or work.
Staff experiences of supported employment with the Sustainable Hub of Innovative Employment for people with Complex needs
Authors: Gore Nick J. , Forrester‐Jones Rachel , Young Rhea
Published: May 2013

Accessible Summary

Many people with learning disabilities want to work.

The Sustainable Hub of Innovative Employment for people with Complex needs (SHIEC) project is about supporting people with complex needs to find work.

This study interviewed staff members who are part of SHIEC.

Staff said it can be difficult to help people with complex needs to find work and this often made them worried.

Staff also said that when people with complex needs found work, it was very rewarding.

Staff said being part of SHIEC helped them do this.

Whilst the value of supported employment for people with learning disabilities is well substantiated, the experiences of supporting individuals into work are less well documented. The Sustainable Hub of Innovative Employment for people with Complex needs aims to support people with learning disabilities and complex needs to find paid employment. Sixteen semi‐structured interviews administered to staff members of Sustainable Hub of Innovative Employment for people with Complex needs revealed seven core themes concerning their experiences of helping people with complex needs into work. This included the practical and emotional reality of facilitating supported employment and a reflection on those factors that influenced success. This article discusses how findings relate more broadly to work in this area, and the vital roles frontline staff play in making employment happen for people with learning disabilities.
Nuclear MMP‐9 role in the regulation of rat skeletal myoblasts proliferation
Authors: Zimowska Malgorzata , Swierczynska Marta , Ciemerych Maria A.
Published: May 2013

Background information

Matrix metalloproteinases (MMPs) are the key enzymes responsible for the remodelling of extracellular matrix. Two of them, namely MMP‐2 and MMP‐9 (gelatinases A and B, respectively), are expressed in skeletal muscles and are involved in their regeneration after the injury. Although MMPs are primarily known to act extracellularly, recent studies have shown that some of them are also found within the cell. In this study, we examine intracellular localisation of gelatinases during myoblasts differentiation in vitro, focussing the impact of MMPs inhibition on the myoblasts proliferation and function.

Results

We show that MMP‐9 localises within the S‐phase nuclei of in vitro differentiating myoblasts. The inhibition of MMPs activity achieved by either doxycycline (a non‐competitive inhibitor of collagenases), TIMP‐1 (tissue inhibitor of metalloproteinases 1) or neutralising anti‐MMP‐9 antibody affects nuclear localisation of this gelatinase, and impacts at myoblasts proliferation.

Conclusions

During myoblasts differentiation, MMP‐9 that is localised in nuclei might be involved in the processes regulating cell cycle progression.
Pituitary dysfunction after traumatic brain injury in children: is there a need for ongoing endocrine assessment?
Authors: Casano‐Sancho Paula , Suárez Larisa , Ibáñez Lourdes , García‐Fructuoso Gemma , Medina Julita , Febrer Anna
Published: May 2013

Background

Hypopituitarism has been widely described in adults after traumatic brain injury (TBI); however, the available data in paediatric populations are scarce. Here, we report the results of a prospective, long‐term study in children, adolescents and young adults.

Study group

Thirty‐seven children (age, 2 months to 19·9 years) of 51 eligible patients were followed for 1 year. Clinical and baseline endocrine variables were assessed in all 3 and 12 months after TBI; children ≥ 6 years underwent two stimulation tests (glucagon stimulation and megatest).

Results

In the group ≥6 years, 11 of 23 patients (47·8%) had a subnormal GH peak 3 months after TBI that persisted in 8 of 23 patients (34%) after 1 year. The GH response showed no correlation with injury severity (GCS, Marshall classification). Growth velocity was normal in all patients, except for one. Body mass index (BMI) SDS increased significantly in the group with low GH response. A suboptimal cortisol was observed in 10 of 23 subjects, which normalized in all but three, 1 year thereafter. All patients but one showed a pubertal response to GnRH testing. No clinical or hormonal abnormalities were detectable in children <6 years.

Conclusion

Our results recommend to prospectively follow children after TBI: firstly, because the impairment of pituitary function cannot be predicted, and secondly, to avoid the potential consequences of pituitary dysfunction. Prospective clinical trials are needed before recommending a systematic screening after TBI and/or GH therapy either in postpubertal children or in prepubertal children who grow normally.
Heart rate variability in pubertal girls with type 1 diabetes: its relationship with glycaemic control, insulin resistance and hyperandrogenism
Authors: Cho Yoon Hi , Craig Maria E. , Srinivasan Shubha , Benitez‐Aguirre Paul , Mitchell Paul , Jopling Tracey , Donaghue Kim C.
Published: May 2013

Objective

To examine the association between glycaemic control, insulin resistance and hyperandrogenism on cardiac autonomic function in peripubertal girls with type 1 diabetes.

Design

Prospective, clinic‐based study of 125 girls with diabetes and 46 age‐matched nondiabetic girls.

Measurements

Heart rate variability (HRV) parameters derived from a 10‐min ECG recording using LabChart Pro were as follows: standard deviation of mean NN intervals (SDNN), where NN = adjacent QRS complexes; root mean squared difference of successive NN intervals (RMSSD) – estimates of overall HRV; and low‐/high‐frequency (LF:HF) ratio – an estimate of the sympathovagal balance. Androgens and sex hormone binding globulin (SHBG) were measured in girls with diabetes, and free androgen index (FAI) calculated. HRV and anthropometry were measured in nondiabetic controls.

Results

Adolescents with diabetes (median age 15·1 years [13·3–16·0], diabetes duration 7·0 years [4·6–10·0] and median HbA1c 8·4% [7·5–9·3]) had higher HR and lower HRV compared with controls. Using multivariate models in the diabetes group, higher HR was associated with higher HbA1c, total daily dose insulin/kg body weight and systolic BP standard deviation scores (SDS), whilst reduced HRV was associated with higher HbA1c (SDNN, RMSSD and LF:HF ratio), lower SHBG (SDNN and RMSSD) and higher weight SDS (LF:HF ratio). Higher FAI was associated with higher HR and reduced HRV measures in the univariate analyses only.

Conclusions

In adolescent girls with diabetes, reduced HRV parameters are associated with worse glycaemic control, lower SHBG and higher weight SDS. SHBG should be considered in the cardiac risk models for this population.
Finite Element Image Warping
Authors: Kaufmann Peter , Wang Oliver , Sorkine‐Hornung Alexander , Sorkine‐Hornung Olga , Smolic Aljoscha , Gross Markus
Published: May 2013

We introduce a single unifying framework for a wide range of content‐aware image warping tasks using a finite element method (FEM). Existing approaches commonly define error terms over vertex finite differences and can be expressed as a special case of our general FEM model. In this work, we exploit the full generality of FEMs, gaining important advantages over prior methods. These advantages include arbitrary mesh connectivity allowing for adaptive meshing and efficient large‐scale solutions, a well‐defined continuous problem formulation that enables clear analysis of existing warping error functions and allows us to propose improved ones, and higher order basis functions that allow for smoother warps with fewer degrees of freedom. To support per‐element basis functions of varying degree and complex mesh connectivity with hanging nodes, we also introduce a novel use of discontinuous Galerkin FEM. We demonstrate the utility of our method by showing examples in video retargeting and camera stabilization applications, and compare our results with previous state of the art methods.
Photon Parameterisation for Robust Relaxation Constraints
Authors: Spencer B. , Jones M.W.
Published: May 2013

This paper presents a novel approach to detecting and preserving fine illumination structure within photon maps. Data derived from each photon's primal trajectory is encoded and used to build a high‐dimensional kd‐tree. Incorporation of these new parameters allows for precise differentiation between intersecting ray envelopes, thus minimizing detail degradation when combined with photon relaxation. We demonstrate how parameter‐aware querying is beneficial in both detecting and removing noise. We also propose a more robust structure descriptor based on principal components analysis that better identifies anisotropic detail at the sub‐kernel level. We illustrate the effectiveness of our approach in several example scenes and show significant improvements when rendering complex caustics compared to previous methods.