bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative genetics of basal metabolic rate and body mass in free‐living pied flycatchers
Authors: Bushuev A. V. , Husby A. , Sternberg H. , Grinkov V. G. 
Published: July 2012

AbstractDespite basal metabolic rate (BMR) being one of the most commonly measured physiological traits and an important indicator of competitive ability, very little is known about its genetic basis and relation to other physiological traits. Here, we present the first attempt to estimate the multivariate basis of BMR using a natural population of pied flycatcher Ficedula hypoleuca breeding in the Tomsk Region, Western Siberia. We show relatively high and significant heritability of whole‐organism BMR, mass‐specific BMR and mass‐independent BMR (h
2 = 0.43, 0.55 and 0.52, respectively), which indicates the potential of these energetic traits to respond to direct selection. In contrast to some previous reports, we found that the genetic correlations between body mass and all three measures of BMR were not significantly different from zero. Independent evolution of body mass and BMR in this species should therefore be possible. Following a previous report, we also estimated the genetic correlations between the different BMR measures and show they are all close to unity, suggesting that they are, from a genetic point of view, a similar trait. Our results are in contrast with previous studies measuring the genetic basis of metabolic rates using aviary‐bred birds and highlight the importance of considering BMR in a natural setting.
Proteomic analysis of mouse brain cortex identifies metabolic down‐regulation as a general feature of ischemic pre‐conditioning
Authors: Scornavacca Giacomo , Gesuete Raffaella , Orsini Franca , Pastorelli Roberta , Fanelli Roberto , de Simoni Maria‐Grazia , Airoldi Luisa 
Published: July 2012

J. Neurochem. (2012) 122, 1219–1229.AbstractThe molecular mechanisms that lead to ischemic pre‐conditioning are not completely understood, and proteins are important players. We compared the mouse brain cortex proteome from different ischemia sets: transient (7 min) middle cerebral artery occlusion (7′MCAo, pre‐conditioning stimulus), permanent MCAo (pMCAo, severe ischemia), and pMCAo 4 days after 7′MCAo (7′MCAo/pMCAo, pre‐conditioned model). Proteins were analyzed by two‐dimensional electrophoresis coupled to liquid chromatography–tandem mass spectrometry. Overall, 28 proteins were expressed differentially from sham controls, and identified. The ischemic pre‐conditioning stimulus alone up‐regulated the stress protein heat‐shock protein 70 (HSP70), possibly activated by the androgen receptor. Western blotting confirmed the increased expression of HSP70 and showed that androgen receptor expression paralleled that of HSP70. In the ischemic‐tolerant group (7′MCAo/pMCAo), a number of proteins over‐expressed after pMCAo returned to sham levels, seven proteins remained up‐regulated as in pMCAo, and five proteins mainly involved in energy metabolism and mitochondrial electron transport and unchanged in pMCAo were down‐regulated only in ischemic tolerance, suggesting a role in brain pre‐conditioning. Astrocytes participated in ischemic‐tolerance induction, as shown by the down‐regulation of glutamine synthetase in the 7′MCAo/pMCAo group. The results suggest that metabolic down‐regulation was a general feature of ischemic pre‐conditioning, playing a pivotal role in neuroprotection.
A new model of autism spectrum disorder assessment and diagnosis by multiagency community‐based teams in primary schools
Authors: Simpson Wendy , Brown Carolyn , Nisbet Nara , Metcalfe Ruth , Claisse Zoe , Watson Lorna 
Published: July 2012

BackgroundNational guidelines stress the importance of early diagnosis of autism spectrum disorder (ASD). This pilot investigated the feasibility and acceptability of assessing children in their community.MethodThe pilot study was carried out from August 2007 to January 2009, and the roll‐out of the programme started in 2010 and is currently underway. Workers undertook assessments and made a group decision about diagnosis; participant observation of these team meetings explored the decision‐making process. Semistructured interviews and focus groups explored the views of parents and professionals.ResultsSeventeen children took part in the study: six were diagnosed with ASD; three as not ASD, and eight were referred for further assessment. The model was found acceptable to parents and workers.ConclusionsWith detailed consideration of administration, information, communication and training requirements, this approach has the potential to increase early diagnosis of ASD and reduce demand for specialist assessment.
Are U.S. Multinational Corporations Becoming More Aggressive Income Shifters?
Authors: KLASSEN KENNETH J. , LAPLANTE STACIE K. 
Published: July 2012

ABSTRACTThis paper examines income shifting of U.S. multinational companies over the past two decades. Domestic and foreign policy makers are increasingly concerned with the effect of income shifting on dwindling tax revenues, however, extant research on income shifting by U.S. multinational enterprises is mixed. We address the disconnect between the academic literature and the policy maker's perceptions by examining the extent of multijurisdictional income shifting by U.S. multinational companies. We directly address conflicting results in extant literature and show that using either multiperiod proxies or instrumental variables overcomes weaknesses of annual proxies in this setting. Our tests show that U.S. companies have become more active at shifting income out of the United States as the regulatory costs of shifting have changed. Holding tax rate differences between U.S. and foreign jurisdictions constant, our empirical estimates suggest that our sample of 380 corporations with low average foreign tax rates collectively shifts approximately $10 billion of additional income out of the United States annually during 2005–2009 relative to 1998–2002 due to varying regulatory costs of shifting.
The Information Content of Tax Expense for Firms Reporting Losses
Authors: DHALIWAL DAN S. , KAPLAN STEVEN E. , LAUX RICK C. , WEISBROD ERIC 
Published: July 2012

ABSTRACTWe investigate whether management's decision regarding the recognition of the valuation allowance (VA) for deferred tax assets provides incremental information about the persistence of accounting losses. We introduce a classification scheme that assigns loss firm‐years into three categories based on whether management appears to have recognized a material change in the VA, and whether or not the firm has positive taxable income (e.g., a net operating loss). The results of our study show that our tax categories contain information about the persistence of accounting losses over the following three years beyond variables previously identified to predict loss persistence. This incremental information is consistent with management using private information about the firm's future prospects in setting the VA. Finally, we find that investors’ pricing of the VA varies with the saliency of the tax signal and the information environment of the firm.
Biofeedback Therapy for Pediatric Headache: Factors Associated With Response
Authors: Blume Heidi K. , Brockman Libby N. , Breuner Cora C. 
Published: July 2012

Objectives.— The goal of this study was to measure the effect of biofeedback therapy on pediatric headache and to identify factors associated with response to biofeedback therapy.Background.— In the United States, 17% of children have frequent or severe headaches. Biofeedback therapy (BFT) appears to be an effective treatment for headaches in adults and is often recommended for children with headaches, but there are few data in the pediatric population. It is also not clear which patients are most likely to benefit from biofeedback therapy.Methods.— We examined the records of patients, aged 8 to 18 years old, who were referred to a pediatric BFT clinic for management of headache between 2004 and 2008. We extracted data regarding patient and headache characteristics, medication use, family history, and measures of depression, anxiety, and somatization. Chronic headache was defined as ≥4 headache days/week. Positive response to biofeedback was defined as a 50% reduction in number of headache days/week or hours/week, or ≥3‐point decrease in severity (0‐10 scale) between first and last visits. We analyzed the responder rate for those with episodic and chronic headaches and performed multivariable analysis to determine what factors were associated with headache response to biofeedback therapy.Results.— We analyzed records from 132 children who attended ≥2 biofeedback sessions. Median headache frequency dropped from 3.5 to 2 headache days/week between the first and last visits. The response rate was 58% overall; 48% for chronic headaches and 73% episodic headaches. In multivariate analysis, ability to raise hand temperature by >3°F at the last visit and use of selective serotonin reuptake inhibitors (SSRIs) were associated with a positive response, and preventive medication use was associated with nonresponse. Anxiety, depression, and somatization were not significantly associated with response to biofeedback therapy.Conclusions.— Biofeedback therapy appears to be an effective treatment for children and adolescents with both episodic and chronic headaches. Further study is warranted to compare biofeedback with other treatments for chronic pediatric headache. Use of SSRIs appears to be associated with a positive response to biofeedback therapy, but the reasons for this relationship are unclear and merit further study.
Multinational assessment of blood‐borne virus testing and transfusion safety on the African continent
Authors: Laperche Syria ,   Francophone African Group for Research in Blood Transfusion
Published: July 2012

BACKGROUND: Failures of blood screening due to low test quality or poor laboratory technique increase the risk of transfusion‐transmitted infections. For this reason, the World Health Organization has recommended a quality control (QC) system for African blood centers.STUDY DESIGN AND METHODS: We conducted a cross‐sectional research assessment of test performance at 51 blood centers in 17 African countries. A blinded, standardized panel containing 25 samples positive for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) and negative controls was tested by the centers using their operational infectious disease testing consisting of rapid tests, enzyme immunoassays (EIAs), or antigen‐antibody EIAs. Nucleic acid testing was not performed.RESULTS: The overall performances of the 42 assays were the lowest for hepatitis B surface antigen (75.6% sensitivity, 94.5% specificity), then for HCV (80.0% sensitivity, 98.1% specificity) and for HIV (81.4% sensitivity, 99.6% specificity). Poor sensitivity was driven by the use of rapid tests, which had sensitivities of 47.4% for HBV, 63.7% for HCV, and 72.4% for HIV. From a blood screening point of view, 321 (5.6%) infected units would have been transfused due to false‐negative results. Assuming that those that were missed by rapid tests (84%) would have been detected by EIAs, 270 viral contaminations (92 HIV, 65 HCV, and 113 HBV) would have been avoided.CONCLUSION: These results support the discontinuation of rapid tests and implementation of antigen‐antibody EIAs whenever possible in Africa. This successful QC program highlights the need for promoting such periodic external quality assessment studies.
Akt‐ and Erk‐mediated regulation of proliferation and differentiation during PDGFRβ‐induced MSC self‐renewal
Authors: Gharibi Borzo , Ghuman Mandeep S. , Hughes Francis J. 
Published: July 2012

AbstractUnderstanding the mechanisms that direct mesenchymal stem cell (MSC) self‐renewal fate decisions is a key to most tissue regenerative approaches. The aim of this study here was to investigate the mechanisms of action of platelet‐derived growth factor receptor β (PDGFRβ) signalling on MSC proliferation and differentiation. MSC were cultured and stimulated with PDGF‐BB together with inhibitors of second messenger pathways. Cell proliferation was assessed using ethynyl‐2′‐deoxyuridine and phosphorylation status of signalling molecules assessed by Western Blots. To assess differentiation potentials, cells were transferred to adipogenic or osteogenic media, and differentiation assessed by expression of differentiation association genes by qRT‐PCR, and by long‐term culture assays. Our results showed that distinct pathways with opposing actions were activated by PDGF. PI3K/Akt signalling was the main contributor to MSC proliferation in response to activation of PDGFRβ. We also demonstrate a negative feedback mechanism between PI3K/Akt and PDGFR‐β expression. In addition, PI3K/Akt downstream signal cascades, mTOR and its associated proteins p70S6K and 4E‐BP1 were involved. These pathways induced the expression of cyclin D1, cyclin D3 and CDK6 to promote cell cycle progression and MSC proliferation. In contrast, activation of Erk by PDGFRβ signalling potently inhibited the adipocytic differentiation of MSCs by blocking PPARγ and CEBPα expression. The data suggest that PDGFRβ‐induced Akt and Erk pathways regulate opposing fate decisions of proliferation and differentiation to promote MSC self‐renewal. Thus, activation of multiple intracellular cascades is required for successful and sustainable MSC self‐renewal strategies.
Neddylation dysfunction in Alzheimer's disease
Authors: Chen Yuzhi , Neve Rachael L. , Liu Helena 
Published: July 2012

AbstractUbiquitin‐dependent proteolysis is a major mechanism that downregulates misfolded proteins or those that have finished a programmed task. In the last two decades, neddylation has emerged as a major regulatory pathway for ubiquitination. Central to the neddylation pathway is the amyloid precursor protein (APP)‐binding protein APP‐BP1, which together with Uba3, plays an analogous role to the ubiquitin‐activating enzyme E1 in nedd8 activation. Activated nedd8 covalently modifies and activates a major class of ubiquitin ligases called Cullin‐RING ligases (CRLs). New evidence suggests that neddylation also modifies Type‐1 transmembrane receptors such as APP. Here we review the functions of neddylation and summarize evidence suggesting that dysfunction of neddylation is involved in Alzheimer's disease.
Equilibrium binding and kinetic characterization of putative tetracycline repressor family transcription regulator Fad35R from Mycobacterium tuberculosis
Authors: Anand Sushma , Singh Vijay , Singh Appu Kumar , Mittal Monica , Datt Manish , Subramani Bala , Kumaran Sangaralingam 
Published: July 2012

Fatty acids play critical role in the survival and virulence of Mycobacterium tuberculosis (Mtb). Activation of fatty acids by acyl‐CoA synthetases (Fad) into fatty acyl‐CoA is the first and one of the crucial steps in fatty acid metabolism. Mtb possesses 36 fatty acyl‐CoA synthetases, unlike Escherichia coli, which has single enzyme. However, the mechanisms by which the expression of these multiple Fad genes is regulated remain uncharacterized. We characterized the DNA‐ and ligand‐binding properties of a putative tetracycline repressor family regulator, named Fad35R, located upstream of the Fad35 gene and ScoA‐citE operon. We identified a palindromic regulatory motif upstream of Fad35 and characterized the binding of Fad35R to this motif. Equilibrium binding studies show that Fad35R binds to this motif with high affinity (Kd∼ 0.033 μm) and the specificity of binding was confirmed by an electromobility gel shift assay. Kinetic studies indicate that faster association (ka,avg∼ 5.4 × 104 m−1·s−1) and slower dissociation rates (kd,avg∼ 5.84 × 10−4 s−1) confer higher affinity. The affinity for the promoter is maximum at 300 mm NaCl but decreases rapidly beyond this range. Ligand‐binding studies indicate that Fad35R binds specifically to tetracycline and also binds to fatty acid derivatives. The promoter‐binding affinity is decreased significantly in the presence of palmityl‐CoA, suggesting that Fad35R can sense the levels of activated fatty acids and alter its DNA‐binding activity. Our results suggest that Fad35R may be the functional homologue of FadR and controls the expression of genes in a metabolite‐dependent manner.Structured digital abstract
Fad35R binds to palindromic sequence shown by surface plasmon resonance
Fad35R binds to tetracycline and activated fatty acids as shown by fluorescence spectroscopy
N‐linked glycosylation of dimeric acetylcholinesterase in erythrocytes is essential for enzyme maturation and membrane targeting
Authors: Luk Wilson K. W. , Chen Vicky P. , Choi Roy C. Y. , Tsim Karl W. K. 
Published: July 2012

Acetylcholinesterase (AChE) is well‐known for its cholinergic functions in the nervous system; however, this enzyme is also found in other tissues where its function is still not understood. AChE is synthesized through alternative splicing as splicing variants, with isoforms including read‐through (AChER), tailed (AChET) and hydrophobic (AChEH). In human erythrocytes, AChEH is a glycophosphatidylinositol‐linked dimer on the plasma membrane. Three N‐linked glycosylation sites have been identified in the catalytic domain of human AChE. Here, we investigate the roles of glycosylation in assembly and trafficking of human AChEH. In transfected fibroblasts, expression of AChEH was able to mimic the function of the dimeric form of AChE on the erythrocyte membrane. A glycan‐depleted form was constructed by site‐directed mutagenesis. By comparison with the wild‐type AChEH, the mutant had a much lower enzymatic activity and a much higher Km value. In addition, the mutant was dimerized in the endoplasmic reticulum, but was not trafficked to the Golgi apparatus. The results suggest that the glycosylation may affect AChEH enzymatic activity and trafficking, but not dimer formation. The present findings indicate the significance of N‐glycosylation in controlling the biosynthesis of the AChEH dimer form.Structured digital abstract
AChE‐H and GM130 colocalize by cosedimentation through density gradient (View interaction)
AChE‐H and Calnexin colocalize by cosedimentation through density gradient (View interaction)
Influence of Seasonal Variations in Soil Water Availability on Gas Exchange of Tropical Canopy Trees
Authors: Stahl Clément , Burban Benoit , Wagner Fabien , Goret Jean‐Yves , Bompy Félix , Bonal Damien 
Published: July 2012

AbstractSeasonal variations in environmental conditions influence the functioning of the whole ecosystem of tropical rain forests, but as yet little is known about how such variations directly influence the leaf gas exchange and transpiration of individual canopy tree species. We examined the influence of seasonal variations in relative extractable water in the upper soil layers on predawn leaf water potential, saturated net photosynthesis, leaf dark respiration, stomatal conductance, and tree transpiration of 13 tropical rain forest canopy trees (eight species) over 2 yr in French Guiana. The canopies were accessed by climbing ropes attached to the trees and to a tower. Our results indicate that a small proportion of the studied trees were unaffected by soil water depletion during seasonal dry periods, probably thanks to efficient deep root systems. The trees showing decreased tree water status (i.e., predawn leaf water potential) displayed a wide range of leaf gas exchange responses. Some trees strongly regulated photosynthesis and transpiration when relative extractable water decreased drastically. In contrast, other trees showed little variation, thus indicating good adaptation to soil drought conditions. These results have important applications to modeling approaches: indeed, precise evaluation and grouping of these response patterns are required before any tree‐based functional models can efficiently describe the response of tropical rain forest ecosystems to future changes in environmental conditions.
Purinergic signalling – a possible mechanism for KCNQ1 channel response to cell volume challenges
Authors: Hammami S. , Willumsen N. J. , Meinild A.‐K. , Klaerke D. A. , Novak I. 
Published: July 2012

AbstractAimA number of K+ channels are regulated by small, fast changes in cell volume. The mechanisms underlying cell volume sensitivity are not known, but one possible mechanism could be purinergic signalling. Volume activated ATP release could trigger signalling pathways that subsequently lead to ion channel stimulation and cell volume back‐regulation. Our aim was to investigate whether volume sensitivity of the voltage‐gated K+ channel, KCNQ1, is dependent on ATP release and regulation by purinergic signalling.MethodsWe used Xenopus oocytes heterologously expressing human KCNQ1, KCNE1, water channels (AQP1) and P2Y2 receptors. ATP release was monitored by a luciferin–luciferase assay and ion channel conductance was recorded by two‐electrode voltage clamp.ResultsThe luminescence assay showed that oocytes released ATP in response to mechanical, hypoosmotic stimuli and hyperosmotic stimuli. Basal ATP release was approx. three times higher in the KCNQ1 + AQP1 and KCNQ1 injected oocytes compared to the non‐injected ones. Exogenously added ATP (0.1 mm) did not have any substantial effect on volume‐induced KCNQ1 currents. Nevertheless, apyrase decreased all currents by about 50%. Suramin inhibited about 23% of the KCNQ1 volume sensitivity. Expression of P2Y2 receptors stimulated endogenous Cl− channels, but it also led to 68% inhibition of the KCNQ1 currents. Adenosine (0.1 mm) also inhibited the KCNQ1 currents by about 56%.ConclusionXenopus oocytes release ATP in response to mechanical stimuli and cell volume changes. Purinergic P2 and P1 receptors confer some of the KCNQ1 channel volume sensitivity, although endogenous adenosine receptors and expressed P2Y2 receptors do so in the negative direction.
Sporicidal Effects of High‐Intensity 405 nm Visible Light on Endospore‐Forming Bacteria
Authors: Maclean Michelle , Murdoch Lynne E. , MacGregor Scott J. , Anderson John G. 
Published: July 2012

AbstractResistance of bacterial endospores to treatments, including biocides, heat and radiation is a persistent problem. This study investigates the susceptibility of Bacillus and Clostridium endospores to 405 nm visible light, wavelengths which have been shown to induce inactivation of vegetative bacterial cells. Suspensions of B. cereus endospores were exposed to high‐intensity 405 nm light generated from a light‐emitting diode array and results demonstrate the induction of a sporicidal effect. Up to a 4‐log10 CFU mL−1 reduction in spore population was achieved after exposure to a dose of 1.73 kJ cm−2. Similar inactivation kinetics were demonstrated with B. subtilis, B. megaterium and C. difficile endospores. The doses required for inactivation of endospores were significantly higher than those required for inactivation of B. cereus and C. difficile vegetative cells, where ca 4‐log10 CFU mL−1 reductions were achieved after exposure to doses of 108 and 48 J cm−2, respectively. The significant increase in dose required for inactivation of endospores compared with vegetative cells is unsurprising due to the notorious resilience of these microbial structures. However, the demonstration that visible light of 405 nm can induce a bactericidal effect against endospores is significant, and could have potential for incorporation into decontamination methods for the removal of bacterial contamination including endospores.