bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rational Design of Substrate‐Based Multivalent Inhibitors of the Histone Acetyltransferase Tip60
Authors: Yang Chao , Ngo Liza , Zheng Y. George 
Published: January 2014

AbstractTip60, the 60 kDa HIV‐1 Tat‐interactive protein, is a key member of the MYST family of histone acetyltransferases (HATs) and plays critical roles in apoptosis and DNA repair. Potent and selective inhibitors of Tip60 are valuable tools for studying the functions of this potential drug target. In this work, we designed, synthesized and evaluated a new set of substrate‐based inhibitors containing multiple binding modalities. In addition to the coenzyme A (CoA) moiety and the histone H3 peptide backbone, mono‐ and tri‐methyl marks were incorporated at Lys 4 and/or Lys 9 sites in the H3 peptide substrate. The biochemical assay results showed that the presence of methyl group(s) on the substrate resulted in more potent inhibitors of Tip60, relative to the parent H3‐CoA bisubstrate inhibitor. Importantly, by comparing the inhibitory properties of the ligands against full‐length Tip60 and the HAT domain, we determined that the K4me1 and K9me3 marks contributed to the potency augmentation by interacting with the catalytic region of the enzyme.
Exchanged Cations and Water during Reactions in Polypyrrole Macroions from Artificial Muscles
Authors: Valero Laura , Otero Toribio F. , Martínez José G. 
Published: January 2014

AbstractThe movement of the bilayer (polypyrrole–dodecylbenzenesulfonate/tape) during artificial muscle bending under flow of current square waves was studied in aqueous solutions of chloride salts. During current flow, polypyrrole redox reactions result in variations in the volumes of the films and macroscopic bending: swelling by reduction with expulsion of cations and shrinking by oxidation with the insertion of cations. The described angles follow a linear function, different in each of the studied salts, of the consumed charge: they are faradaic polymeric muscles. The linearity indicates that cations are the only exchanged ions in the studied potential range. By flow of the same specific charge in every electrolyte, different angles were described by the muscle. The charge and the angle allow the number and volume of both the exchanged cations and the water molecules (related to a reference) between the film to be determined, in addition to the electrolyte per unit of charge during the driving reaction. The attained apparent solvation numbers for the exchanged cations were: 0.8, 0.7, 0.6, 0.5, 0.5, 0.4, 0.25, and 0.0 for Na+, Mg2+, La3+, Li+, Ca2+, K+, Rb+, and Cs+, respectively.
Interface Stability of a TiO2/3‐Methoxypropionitrile‐Based Electrolyte: First Evidence for Solid Electrolyte Interphase Formation and Implications
Authors: Flasque Miguel , Van Nhien Albert Nguyen , Swiatowska Jolanta , Seyeux Antoine , Davoisne Carine , Sauvage Frédéric 
Published: January 2014

AbstractWe report an in‐depth study focusing on the stability of a benchmark electrolyte composition based on a low‐volatile 3‐methoxypropionitrile (MPN) solvent employed in dye‐sensitized solar cells. In the presence of TiO2, the semi‐conductor surface plays a catalytic role in the thermal degradation of the electrolyte, which induces, among other effects, the nucleation and growth of a uniform solid electrolyte interphase (SEI) layer that wraps TiO2. On the basis of our actual understanding, we argue that SEI formation is responsible for triiodide depletion in the electrolyte during ageing and also has a simultaneous impact on TiO2 optoelectronic properties through the onset of a visible‐light absorption tail, energy modification of intraband trap states, and the induction of an increase in both electron lifetime and transport time in TiO2. In‐depth characterization of this layer by using XPS and ToF‐SIMS indicates that the chemical composition of this SEI results from solvent and additive degradation, that is, iodide, sulfur, cyano, nitrogen, carbon, and imidazolium rings. The SEI thickness, its content, and the concentration profile strongly vary depending on the ageing conditions. The outcome of this new finding is discussed in comparison with literature observations and stresses the difficulties in reaching long‐term stability at 85 °C by using MPN‐based electrolytes unless new interfacial engineering is accomplished to impede pinholes between dye molecules on TiO2.
Implementation of a quality improvement initiative in Belgian diabetic foot clinics: feasibility and initial results
Authors: Doggen Kris , Van Acker Kristien , Beele Hilde , Dumont Isabelle , Félix Patricia , Lauwers Patrick , Lavens Astrid , Matricali Giovanni A. , Randon Caren , Weber Eric , Van Casteren Viviane , Nobels Frank ,   On behalf of the Initiative for Quality Improvement and Epidemiology in Diabetic Foot Clinics (IQED‐Foot) Study Group
Published: January 2014

AbstractBackgroundThis article aims to describe the implementation and initial results of an audit–feedback quality improvement initiative in Belgian diabetic foot clinics.MethodsUsing self‐developed software and questionnaires, diabetic foot clinics collected data in 2005, 2008 and 2011, covering characteristics, history and ulcer severity, management and outcome of the first 52 patients presenting with a Wagner grade ≥2 diabetic foot ulcer or acute neuropathic osteoarthropathy that year. Quality improvement was encouraged by meetings and by anonymous benchmarking of diabetic foot clinics.ResultsThe first audit–feedback cycle was a pilot study. Subsequent audits, with a modified methodology, had increasing rates of participation and data completeness.Over 85% of diabetic foot clinics participated and 3372 unique patients were sampled between 2005 and 2011 (3312 with a diabetic foot ulcer and 111 with acute neuropathic osteoarthropathy). Median age was 70 years, median diabetes duration was 14 years and 64% were men. Of all diabetic foot ulcers, 51% were plantar and 29% were both ischaemic and deeply infected. Ulcer healing rate at 6 months significantly increased from 49% to 54% between 2008 and 2011. Management of diabetic foot ulcers varied between diabetic foot clinics: 88% of plantar mid‐foot ulcers were off‐loaded (P10–P90: 64–100%), and 42% of ischaemic limbs were revascularized (P10–P90: 22–69%) in 2011.ConclusionsA unique, nationwide quality improvement initiative was established among diabetic foot clinics, covering ulcer healing, lower limb amputation and many other aspects of diabetic foot care. Data completeness increased, thanks in part to questionnaire revision. Benchmarking remains challenging, given the many possible indicators and limited sample size. The optimized questionnaire allows future quality of care monitoring in diabetic foot clinics. Copyright © 2014 John Wiley & Sons, Ltd.
Establishing a multidisciplinary diabetic foot team in a large tertiary hospital: a workshop
Authors: Cahn Avivit , Elishuv Ofer , Olshtain‐Pops Keren 
Published: January 2014

AbstractEvery year, over 1 million people with diabetes lose a leg due to diabetic foot disease. Most amputations are preceded by a foot ulcer. Causes for the development of foot ulcers are generally multifactorial and may include neuropathy, peripheral vasculopathy, abnormal foot mechanics and infection. Multidisciplinary approach to the patient with acute diabetic foot is mandatory and has been shown to reduce amputation rate. In our article we describe the establishment of a multidisciplinary diabetic foot team in a large tertiary hospital and its outcomes. Copyright © 2014 John Wiley & Sons, Ltd.
The New insights from DPP‐4 inhibitors: their potential immune modulatory function in autoimmune diabetes
Authors: Zhao Yunjuan , Yang Lin , Wang Xiangbing , Zhou Zhiguang 
Published: January 2014

SummaryDipeptidyl peptidase‐4 (DPP‐4) inhibitors are a new class of anti‐diabetic agents that are widely used in clinical practice to improve glycemic control and protect β‐cell function in patients with type 2 diabetes. DPP‐4 is also known as lymphocyte cell surface protein CD26 and plays an important role in T‐cell immunity. Autoimmune diabetes, a T‐cell mediated organ‐specific disease, is initiated by the imbalance between pathogenic and regulatory T‐lymphocytes. DPP‐4 inhibitors can suppress pathogenic effects of Th1 and Th17 cells and up‐regulate Th2 cells and regulatory T cells, which play a critical role in ameliorating autoimmune diabetes. This provides a basis for the potential use of DPP‐4 inhibitors in the treatment of autoimmune diabetes. Recent studies suggest that DPP‐4 inhibitors improve β‐cell function and attenuate autoimmunity in type 1 diabetic mouse models. However, there are few clinical studies on the treatment of autoimmune diabetes with DPP‐4 inhibitors. Further studies are warranted to confirm the therapeutic effects of DPP‐4 inhibitors on autoimmune diabetes in humans. Copyright © 2014 John Wiley & Sons, Ltd.
Distribution and function of TrkB receptors in the developing brain of the opossumMonodelphis domestica
Authors: Bartkowska Katarzyna , Aniszewska Agata , Turlejski Kris , Djavadian Ruzanna L. 
Published: January 2014

ABSTRACTThe expression, development pattern, spatiotemporal distribution, and function of TrkB receptors were investigated during the postnatal brain development of the opossum. Full‐length TrkB receptor expression was detectable in the newborn opossum, whereas three different short forms that are expressed in the adult brain were almost undetectable in the newborn opossum brain. The highest level of full‐length TrkB receptor expression was observed at P35, which corresponds to the time of eye opening. We found that in different brain structures, TrkB receptors were localized in various compartments of cells. The hypothalamus was distinguished by the presence of TrkB receptors not only in cell bodies but also in the neuropil. Double immunofluroscent staining for TrkB and a marker for the identification of the cell phenotype in several brain regions such as the olfactory bulb, hippocampus, thalamus, and cerebellum showed that unlike in eutherians, in the opossum, TrkB receptors were predominantly expressed in neurons. A lack of TrkB receptors in glial cells, particularly astrocytes and oligodendrocytes, provides evidence that TrkB receptors can play a functionally different role in marsupials than in eutherians. The effects of TrkB signaling on the development of cortical progenitor cells were examined in vitro using shRNAs. Blockade of the endogenous TrkB receptor expression induced a decrease in the number of progenitor cells proliferation, whereas the number of apoptotic progenitor cells increased. These changes were statistically significant but relatively small. In contrast, TrkB signaling was strongly involved in regulation of the cortical progenitor cell differentiation process. © 2014 Wiley Periodicals, Inc. Develop Neurobiol 74: 707–722, 2014
Transposon‐dependent induction of Vincent van Gogh's sunflowers: Exceptions revealed
Authors: Fambrini Marco , Salvini Mariangela , Basile Alice , Pugliesi Claudio 
Published: January 2014

SummaryThe radiate sunflower inflorescence is composed by zygomorphic ray flowers and actinomorphic disk flowers. Studies performed on mutants identify HaCYC2c, a CYCLOIDEA (CYC)‐like gene, as one of the key players controlling flower symmetry in sunflower. turf and tub mutants are characterized by a shift from zygomorphic to actinomorphic ray flowers, caused by insertion of transposable elements (TEs) in HaCYC2c gene. In dbl or Chry mutants, an insertion upstream the coding region of HaCYC2c causes the ectopic expression of the gene and the shift from actinomorphic to zygomorphic disk flowers. We focused on Chry2 mutant: a 1034 bp insertion placed 558 bp before the start codon of HaCYC2c was identified. The insertion is a truncated version of a CACTA TE. Unexpectedly, phenotypic and genetic co‐segregation analysis in F2 and F3 progenies derived from the crosses Chry2 × turf and turf × Chry2 demonstrated that CACTA insertion is not always sufficient to alter the expression of HaCYC2c gene and generate Chry2 phenotype. F3 plants homozygous for the CACTA insertion displayed either HaCYC2c transcription pattern identical to wild‐type plants or a normal heterogamous inflorescence. Stated these results, we conclude that a much more complex regulatory system stays behind the Chry2 phenotype. genesis 52:315–327, 2014. © 2014 Wiley Periodicals, Inc.
Disentangling community functional components in a litter‐macrodetritivore model system reveals the predominance of the mass ratio hypothesis
Authors: Bílá Karolína , Moretti Marco , de Bello Francesco , Dias André T.C. , Pezzatti Gianni B. , Van Oosten Arend Raoul , Berg Matty P. 
Published: January 2014

AbstractRecent investigations have shown that two components of community trait composition are important for key ecosystem processes: (i) the community‐weighted mean trait value (CWM), related to the mass ratio hypothesis and dominant trait values in the community, and (ii) functional diversity (FD), related to the complementarity hypothesis and the divergence of trait values. However, no experiments controlling for the inherent dependence betweenCWMandFDhave been conducted so far. We used a novel experimental framework to disentangle the unique and shared effects ofCWMandFDin a leaf litter‐macrodetritivore model system. We manipulated isopod assemblages varying in species number,CWMandFDof litter consumption rate to test the relative contribution of these community parameters in the decomposition process. We showed thatCWM, but also the combination ofCWMandFD, is a main factor controlling litter decomposition. When we tested individual biodiversity components separately,CWMof litter consumption rate showed a significant effect on decomposition, whileFDand species richness alone did not. Our study demonstrated that (i) trait composition rather than species diversity drives litter decomposition, (ii) dominant trait values in the community (CWM) play a chief role in driving ecosystem processes, corroborating the mass ratio hypothesis, and (iii) trait dissimilarity can contribute in modulating the overall biodiversity effects. Future challenge is to assess whether the generality of our finding, that is, that dominant trait values (CWM) predominate over trait dissimilarity (FD), holds for other ecosystem processes, environmental conditions and different spatial and temporal scales.
Evolutionary quantitative genetics of behavioral responses to handling in a wild passerine
Authors: Class Barbara , Kluen Edward , Brommer Jon E. 
Published: January 2014

AbstractBehavioral differences between individuals that are consistent over time characterize animal personality. The existence of such consistency contrasts to the expectation based on classical behavioral theory that facultative behavior maximizes individual fitness. Here, we study two personality traits (aggression and breath rate during handling) in a wild population of blue tits during 2007–2012. Handling aggression and breath rate were moderately heritable (h2 = 0.35 and 0.20, respectively) and not genetically correlated (rA = 0.06) in adult blue tits, which permits them to evolve independently. Reciprocal cross‐fostering (2007–2010) showed that offspring reared by more aggressive males have a higher probability to recruit. In addition, offspring reared by pairs mated assortatively for handling aggression had a higher recruitment probability, which is the first evidence that both parents' personalities influence their reproductive success in the wild in a manner independent of their genetic effects. Handling aggression was not subjected to survival selection in either sex, but slow‐breathing females had a higher annual probability of survival as revealed by capture–mark–recapture analysis. We find no evidence for temporal fluctuations in selection, and thus conclude that directional selection (via different fitness components) acts on these two heritable personality traits. Our findings show that blue tit personality has predictable fitness consequences, but that facultative adjustment of an individual's personality to match the fitness maximum is likely constrained by the genetic architecture of personality. In the face of directional selection, the presence of heritable variation in personality suggests the existence of a trade‐off that we have not identified yet.
Estimated urinary sodium excretion and risk of heart failure in men and women in the EPIC‐Norfolk study
Authors: Pfister Roman , Michels Guido , Sharp Stephen J. , Luben Robert , Wareham Nick J. , Khaw Kay‐Tee 
Published: January 2014

AimsInterventional trials provide evidence for a beneficial effect of reduced dietary sodium intake on blood pressure. The association of sodium intake with heart failure which is a long‐term complication of hypertension has not been examined.Methods and resultsHazard ratios [HRs, 95% confidence interval (CI)] of heart failure comparing quintiles of estimated 24 h urinary sodium excretion (USE) were calculated in apparently healthy men (9017) and women (10 840) aged 39–79 participating in the EPIC study in Norfolk. During a mean follow‐up of 12.9 years, 1210 incident cases of heart failure occurred. Compared with the reference category (128 mmol/day ≤USE ≤148 mmol/day), the top quintile (USE ≥191 mmol/day) was associated with a significantly increased hazard of heart failure (1.32, 1.07–1.62) in multivariable analysis adjusting for age, sex, body mass index, diabetes, cholesterol, social class, educational level, smoking, physical activity, and alcohol consumption, with a marked attenuation (1.21, 0.98–1.49) when further adjusting for blood pressure. The bottom quintile (USE ≤127 mmol/day) was also associated with an increased hazard of heart failure (1.29, 1.04–1.60) in multivariable analysis without relevant attenuation by blood pressure adjustment (1.26, 1.02–1.56), but with substantial attenuation when adjusting for interim ischaemic heart disease and baseline C‐reactive protein levels and exclusion of events during the first 2 years (1.18, 0.96–1.47).ConclusionWe demonstrate a U‐shaped association between USE and heart failure risk in an apparently healthy middle‐aged population. The risk associated with the high range of USE was attenuated after adjustment for blood pressure, whereas the risk associated with the low range of USE was attenuated after adjustment for pre‐existing disease processes.
Sentinel lymph node status in Merkel cell carcinoma of the head and neck: Not a predictor of survival
Authors: Fritsch Valerie A. , Camp E. Ramsay , Lentsch Eric J. 
Published: January 2014

AbstractBackgroundThe effect of sentinel lymph node status on survival in patients with Merkel cell carcinoma (MCC) of the head and neck is uncertain.MethodsWe used the Surveillance Epidemiology and End Results (SEER) database to identify patients with MCC who underwent sentinel lymph node biopsy (SLNB). Clinicopathologic data and disease‐specific survival (DSS) were compared among patients with positive and negative sentinel lymph nodes.ResultsWe identified 721 patients with cutaneous MCC who underwent SLNB, of which 173 (24%) had head and neck MCC. The rate of sentinel lymph node positivity in patients with head and neck MCC was 23.1%. Sentinel lymph node metastasis did not significantly affect survival in head and neck MCC (p = .139).ConclusionUsing the SEER database, we report what we believe to be the largest head and neck MCC study to date. Our results suggest that sentinel lymph node status does not predict survival in head and neck MCC. Independent predictors of MCC‐related mortality seem to be unique in the head and neck region. © 2014 Wiley Periodicals, Inc. Head Neck 36: 571–579, 2014
Insomnia in paediatric chronic pain and its impact on depression and functional disability
Authors: Kanstrup M. , Holmström L. , Ringström R. , Wicksell R.K. 
Published: January 2014

AbstractBackgroundChildren and adolescents attending health care due to chronic pain commonly presents with insomnia. Previous research suggests that problems with sleep are associated with depression and functional disability. However, more research is needed to clarify the relationship between pain, insomnia and disability.ObjectiveThis study aims to investigate the frequency, severity and importance of insomnia in paediatric patients with chronic pain and to evaluate the mediating role of insomnia in explaining the relationship between pain and depression as well as between pain and functioning. In addition, to ascertain the adequacy of using a Swedish translation of the Insomnia Severity Index (ISI) with youths, analyses included a statistical evaluation of the instrument.MethodCorrelational analyses of cross‐sectional data from 154 consecutive paediatric patients with chronic pain referred to a tertiary pain clinic.ResultsInsomnia explained a significant amount of variance in depression and functional disability when controlling for demographic characteristics and pain. Indirect effects of insomnia were found for both the relationship between pain and depression, and between pain and functional disability. ISI showed satisfactory psychometric properties in this sample, including internal consistency and concurrent criteria validity.ConclusionsInsomnia is highly important in explaining depression and functional disability in paediatric chronic pain and can be adequately assessed using the ISI.
Missing in Asynchronicity: A Kalman‐em Approach for Multivariate Realized Covariance Estimation
Authors: Corsi Fulvio , Peluso Stefano , Audrino Francesco 
Published: January 2014

SummaryMotivated by the need for a positive‐semidefinite estimator of multivariate realized covariance matrices, we model noisy and asynchronous ultra‐high‐frequency asset prices in a state‐space framework with missing data. We then estimate the covariance matrix of the latent states through a Kalman smoother and expectation maximization (KEM) algorithm. Iterating between the two EM steps, we obtain a covariance matrix estimate which is robust to both asynchronicity and microstructure noise, and positive‐semidefinite by construction. We show the performance of the KEM estimator using extensive Monte Carlo simulations that mimic the liquidity and market microstructure characteristics of the S&P 500 universe as well as in a high‐dimensional application on US stocks. KEM provides very accurate covariance matrix estimates and significantly outperforms alternative approaches recently introduced in the literature. Copyright © 2014 John Wiley & Sons, Ltd.