bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma Carboxymethyl‐Lysine, an Advanced Glycation End Product, and All‐Cause and Cardiovascular Disease Mortality in Older Community‐Dwelling Adults
Authors: Semba Richard D. , Bandinelli Stefania , Sun Kai , Guralnik Jack M. , Ferrucci Luigi
Published: August 2009

OBJECTIVES: To determine whether older adults with high plasma carboxymethyl‐lysine (CML), an advanced glycation end product, are at higher risk of all‐cause and cardiovascular disease (CVD) mortality.

DESIGN: Prospective cohort study.

SETTING: Population‐based sample of adults aged 65 and older residing in Tuscany, Italy.

PARTICIPANTS: One thousand thirteen adults participating in the Invecchiare in Chianti study.

MEASUREMENTS: Anthropometric measures, plasma CML, fasting plasma total, high‐density and low‐density lipoprotein cholesterol, triglycerides, glucose, creatinine. Clinical measures: medical assessment, diabetes mellitus, hypertension, coronary heart disease, heart failure, stroke, cancer. Vital status measures: death certificates and causes of death according to the International Classification of Diseases. Survival methods were used to examine the relationship between plasma CML and all‐cause and CVD mortality, adjusting for potential confounders.

RESULTS: During 6 years of follow‐up, 227 (22.4%) adults died, of whom 105 died with CVD. Adults with plasma CML in the highest tertile had greater all‐cause (hazard ratio (HR)=1.84, 95% confidence interval) CI)=1.30–2.60, P<.001) and CVD (HR=2.11, 95% CI=1.27–3.49, P=.003) mortality than those in the lower two tertiles after adjusting for potential confounders. In adults without diabetes mellitus, those with plasma CML in the highest tertile had greater all‐cause (HR=1.68, 95% CI=1.15–2.44, P=.006) and CVD (HR=1.74, 95% CI=1.00–3.01, P=.05) mortality than those in the lower two tertiles after adjusting for potential confounders.

CONCLUSION: Older adults with high plasma CML are at higher risk of all‐cause and CVD mortality.
Force Needed to Separate Acrylic Resin from Primed and Unprimed Frameworks of Different Designs
Authors: Lee Grace , Engelmeier Robert L. , Gonzalez Maria , Powers John M. , Perezous Leticia F. , O’Keefe Kathy L.
Published: August 2009

Purpose: Poor mechanical and chemical bondings at the interface between a framework and denture base resin have been responsible for many removable partial denture failures. This study tested the force necessary to separate acrylic resin bases from test frameworks using different acrylic retention designs (smooth metal plate, metal plate with bead retention, lattice retention, and mesh retention). The force needed to separate acrylic resin from primed test frameworks was also measured.

Materials and Methods: Eighty chromium‐cobalt test frameworks were fabricated using preformed wax patterns and cast according to manufacturer's instructions. Half the specimens were primed prior to acrylic processing. The same base acrylic was used for all specimens. Separation forces that fractured acrylic resin from test frameworks were generated by a universal testing machine at a crosshead speed of 25 mm/min. Loads at failure and types of failure were recorded. Data were analyzed using ANOVA.

Results: The mean separation force of acrylic resin from unprimed retention designs was highest for the metal plate with beads (3.1 kN), followed by mesh (2.8 kN) and lattice (2.1 kN), and lowest (0.1 kN) for the smooth metal plate. The mean separation force for primed acrylic retention designs was highest for the metal plate with beads (4.2 kN), followed by mesh (3.4 kN) and smooth metal plate (3.0 kN), and lowest for lattice retention (2.6 kN). Bond failure occurred both adhesively at the interface between metal and acrylic resin and cohesively within the acrylic resin. Cohesive bond failure increased when specimens were primed. The rate of cohesive bond failure remained the same for primed mesh retention specimens.

Conclusions: Significantly increased force was necessary to separate the acrylic from each design of primed test specimens compared with unprimed specimens of the same design. The primed metal plate with beads exhibited significantly greater separation force than the other three designs. Primed mesh had significantly greater separation force values than primed lattice and smooth metal plate. Primed lattice was significantly less retentive than the other three primed designs. Except for the retentive mesh specimens, there was higher occurrence of cohesive failures in the acrylic resin when the frameworks were primed.
Comparison of the Passivity between Cast Alloy and Laser‐Welded Titanium Overdenture Bars
Authors: Paiva Jose , Givan Daniel A. , Broome James C. , Lemons Jack E. , McCracken Michael S.
Published: August 2009

Purpose: The purpose of this study was to investigate the fit of cast alloy overdenture and laser‐welded titanium‐alloy bars by measuring induced strain upon tightening of the bars on a master cast as well as a function of screw tightening sequence.

Materials and Methods: Four implant analogs were secured into Type IV dental stone to simulate a mandibular edentulous patient cast, and two groups of four overdenture bars were fabricated. Group I was four cast alloy bars and Group II was four laser‐welded titanium bars. The cast alloy bars included Au–Ag–Pd, Pd–Ag–Au, Au–Ag–Cu–Pd, and Ag–Pd–Cu‐Au, while the laser‐welded bars were all Ti–Al–V alloy. Bars were made from the same master cast, were torqued into place, and the total strain in the bars was measured through five strain gauges bonded to the bar between the implants. Each bar was placed and torqued 27 times to 30 Ncm per screw using three tightening sequences. Data were processed through a strain amplifier and analyzed by computer using StrainSmart software. Data were analyzed by ANOVA and Tukey's post hoc test.

Results: Significant differences were found between alloy types. Laser‐welded titanium bars tended to have lower strains than corresponding cast bars, although the Au–Ag–Pd bar was not significantly different. The magnitudes of total strain were the least when first tightening the ends of the bar.

Conclusions: The passivity of implant overdenture bars was evaluated using total strain of the bar when tightening. Selecting a high modulus of elasticity cast alloy or use of laser‐welded bar design resulted in the lowest average strain magnitudes. While the effect of screw tightening sequence was minimal, tightening the distal ends first demonstrated the lowest strain, and hence the best passivity.
Irving Fisher (1867–1947)
Authors: Tobin James
Published: August 2009

Abstract.  This essay is reprinted from Eatwell, J., M. Milgate and P. Newman (eds.) The New Palgrave: A Dictionary of Economics. 1987, 2: 369–376. United Kingdom, London and Basingstoke: The Macmillan Press Limited; New York, N.Y. The Stockton Press and Japan, Maruzen Company Limited. The essay is reproduced with the kind permission of Palgrave Macmillan.
Irving Fisher of Yale
Authors: Barber William J.
Published: August 2009

Abstract.  An overview of the career and contributions of Irving Fisher.
Fisher's The Nature of Capital and Income*
Authors: Tobin James
Published: August 2009

Abstract.  In this essay James Tobin reminds us of the importance of Irving Fisher's great book and how that book was favorably received by economists. Fisher presented fundamental definitions and supplied a path breaking exposition of the mathematics of interest rates and their relationship to the valuation of assets. This essay was originally published as the “Editorial Introduction to Volume 2 of The Works of Irving Fisher, 14 vols London: Pickering & Chatto, 1997; 2:1–6.
The Ideal Inflation‐Indexed Bond and Irving Fisher's Impatience Theory of Interest with Overlapping Generations*
Authors: Geanakoplos John
Published: August 2009

Abstract  Irving Fisher long advocated inflation‐indexed bonds. But with what index? I prove in the context of a multicommodity CAPM world that the best welfare‐improving bond pays the minimum money needed to achieve the same utility, and not the minimum needed to buy an ideal commodity bundle.

Irving Fisher also developed and advocated the impatience theory of interest. But in OLG economies, the rate of interest is determined by population growth, not impatience. I reconcile this contradiction by proving that in stationary OLG economies with land, the interest rate at the unique steady state does depend on impatience. Indeed, the proposition that greater impatience creates higher interest rates holds more generally in OLG with land than in Fisher's two‐period model, because then income effects and substitution effects naturally work in the same direction.
Index Number Theory Using Differences Rather Than Ratios
Authors: Diewert W. Erwin
Published: August 2009

Abstract  Traditional index number theory decomposes a value ratio into the product of a price index times a quantity index. The price (quantity) index is interpreted as an aggregate price (quantity) ratio. The present paper takes an alternative approach to index number theory, started by Bennet and Montgomery in the 1920s, which decomposes a value difference into the sum of a price difference plus a quantity difference. Axiomatic and economic approaches to this alternative branch of index theory are considered in the present paper. The analysis presented has some relevance to accounting theory in which revenue, cost, or profit changes need to be decomposed into price quantity components or where standard or budgeted performance is compared with actual performance (variance analysis). The methodology presented in the paper is also relevant for consumer surplus analysis.
Perceptions of the Regulated Community in Environmental Policy: The View from Below
Authors: Pautz Michelle C.
Published: August 2009

Discussions in environmental policy often focus on the highest levels of decision making and action while paying scant attention to those individuals on the front lines. Among those frequently overlooked are the individuals at regulated facilities who interact with government regulators on a frequent basis. Interviews with nearly two dozen facility personnel in Virginia yield findings that challenge common perceptions of the relationships between facility personnel and inspectors. In particular, 86 percent of facility personnel, representing a range of regulated facilities from prisons to landfills to dry cleaners, said their interactions with inspectors were positive. Approximately 70 percent of them said that they trust inspectors and provided evidence of trust in their stories. The ramifications of these findings for environmental policy could be potentially significant because facility personnel are presumed to be adversarial, if not outright hostile, and this assumption impacts the design and implementation of environmental regulations.
Climate Change Policy Implementation: A Cross‐Sectional Analysis
Authors: Dolšak Nives
Published: August 2009

Why would countries invest resources to protect the global atmosphere, a global common‐pool resource? After all, this is an open‐access resource with no restrictions on appropriating its benefits. Furthermore, why would they do so under the aegis of a weak global regime (the United Nations Framework Convention on Climate Change, UNFCCC) that has virtually no provisions for sanctioning noncompliance and when the largest contributor to the problem is not participating in the regime? This article examines why a number of countries have implemented the UNFCCC. I hypothesize that countries implement UNFCCC because they corner domestic environmental benefits, namely reduction in local pollution. In my empirical analysis of 127 countries, employing an ordinal logistic regression model, I find that local air pollution is associated with higher levels of implementation of the UNFCCC. Thus, I conclude that the incentives to implement a relatively weak global regime can be found in the domestic political economy.
Developing Durable Infrastructures: Politics, Social Skill, and Sanitation Partnerships in Urban India1
Authors: Gopakumar Govind
Published: August 2009

Accelerated national and international efforts to redress the acute lack of infrastructures in the developing world have focused on forging partnerships to spur infrastructure development. This article finds a sore lack in attempts to grasp how infrastructures implemented through multiactor partnerships within entrenched, often volatile, political environments, become durable. Durability is understood here through field analysis, an approach common within the “new institutional” literature. Two case studies of sanitation infrastructure‐making from cities in India are presented as empirical evidence. Failure of the first case and the success of the second in acquisition of durability clearly illustrate the vital role political strategy plays in making infrastructures durable.
Osteopenia and vitamin D deficiency in children with sickle cell disease
Authors: Chapelon E. , Garabedian M. , Brousse V. , Souberbielle J. C. , Bresson J. L. , De Montalembert M.
Published: August 2009

Objectives:  To assess the prevalence in children with sickle cell disease of low bone mineral density (BMD), a feature found in up to 82% of adults but not well known in children.

Methods:  In 53 children (45 SS, 4 SC, 4 Sβ‐thalassemia) with a mean age of 12.8 ± 2.4 years, we assessed height; weight; sexual maturation; number of hospitalizations, painful crises, and transfusions in the last 3 years; calcium intake; steady‐state hemoglobin and leukocyte count; calcaemia, phosphataemia, and calciuria/creatinuria; serum 25‐(OH)D and PTH concentrations; and osteocalcin, urinary deoxypyridinoline, and the C‐terminal component of pro‐collagen type I. BMD was assessed using dual X‐ray absorptiometry.

Results:  Mean lumbar spine Z‐score was −1.1 ± 1.3 (−3.9 to +1.8). The Z score was significantly lower in girls than in boys in the prepubertal subgroup (−1.74 ± 0.27 vs. −0.53 ± 0.31) (P = 0.0169), but not in the pubertal group (−1.15 ± 0.41 vs. −1.33 ± 0.70). BMD was not associated with any of the disease‐severity markers in girls but was unexpectedly associated with fewer vaso‐occlusive crises and hospitalizations in boys. BMD did not correlate with hemoglobin or leukocyte counts. Vitamin D deficiency [25‐(OH)D < 12 ng/mL] was found in 76% of patients and secondary hyperparathyroidism (PTH > 46 pg/mL) in 38%. BMD was not related to calcium intake, vitamin D status, osteocalcin, or bone resorption markers.

Conclusion:  A slight BMD decrease was found in SCD children, starting before puberty and being more marked in females. The decrease was unrelated to disease severity, vitamin D deficiency, or bone hyperresorption, suggesting abnormal bone formation as the underlying mechanism.
Characterisation of hairy cell leukaemia by tiling resolution array‐based comparative Genome hybridisation: a series of 13 cases and review of the literature
Authors: Nordgren Ann , Corcoran Martin , Sääf Annika , Bremer Anna , Kluin‐Nelemans Hanneke C. , Schoumans Jacqueline , Grandér Dan
Published: August 2009

Little is known about the cytogenetic features and molecular mechanisms behind hairy cell leukaemia (HCL), despite the advances in diagnosis and treatment. Therefore, we used high‐resolution genome‐wide array‐based comparative genomic hybridisation (array‐CGH) and multiplex ligation‐dependent probe amplification (MLPA) to characterise copy number alterations (CNAs) in DNA from 13 cases of HCL. We also summarise CNAs and cytogenetic features in 109 HCL cases comprising our 13 cases and 96 cases from the literature. Genomic array‐CGH revealed imbalances in two out of 13 cases in addition to previously described copy number variants (CNVs) found in healthy individuals. In one case, a 700 kb deletion of 20q11.22 was detected encompassing ten characterised genes, among them the TP53INP2, DNCL2A and ITCH genes. In the second case, trisomy 5, and a deletion of 5p15.2 encompassing a non‐characterised gene AY328033 was found. Altogether only 20/81 (25%) of all cases studied by CGH or gene dose array revealed CNAs. The most common recurrent deletions and breakpoints were 14q22–32 (33%), 6q25 (16%), 2p12 (10%), 22q11 (10%), 17p11–13 (10%), 7q32–36 (9%), 18q11–13 (7%), 1q32–44 (6%), 8p22–23 (6%) and 7q11 (6%). Trisomy 5 occurred in 15%. In addition, several other recurrent breakpoints were identified. Although a number of genomic imbalances were identified in the HCL samples, the genome appeared remarkably stable.
Microtubule Binding and Trapping at the Tip of Neurites Regulate Tau Motion in Living Neurons
Authors: Weissmann Carina , Reyher Hans‐Jürgen , Gauthier Anne , Steinhoff Heinz‐Jürgen , Junge Wolfgang , Brandt Roland
Published: August 2009

During the development of neurons, the microtubule‐associated tau proteins show a graded proximo‐distal distribution in axons. In tauopathies such as Alzheimer's disease, tau accumulates in the somatodendritic compartment. To scrutinize the determinants of tau's distribution and motion, we constructed photoactivatable green fluorescent protein (GFP)‐tagged tau fusion proteins and recorded their distribution after focal activation in living cells. Simulation showed that the motion of tau was compatible with diffusion/reaction as opposed to active transport/reaction. Effective diffusion constants of 0.7–0.8 μm2/second were calculated in neurites of PC12 cells and primary cortical neurons. Furthermore, tau's amino terminal projection domain mediated binding and enrichment of tau at distal neurites indicating that the tip of a neurite acts as an adsorber trapping tau protein. Treatment with taxol, incorporation of disease‐related tau modifications, experimentally induced hyperphosphorylation and addition of preaggregated amyloid β peptides (Aβ) increased the effective diffusion constant compatible with a decreased binding to microtubules. Distal enrichment was present after taxol treatment but was suppressed at disease‐relevant conditions. The data suggest that (i) dynamic binding of tau to microtubules and diffusion along microtubules and (ii) trapping at the tip of a neurite both contribute to its distribution during development and disease.
Association between peer relationship problems and childhood overweight/obesity
Authors: Boneberger Anja , Von Kries Rüdiger , Milde‐Busch Astrid , Bolte Gabriele , Rochat Mascha K. , Rückinger Simon ,   for the GME Study Group
Published: August 2009

Aims:  To assess the association between peer relationship problems and childhood overweight and obesity.

Methods:  Data on 4718 preschool children were obtained at the obligatory school entry health examination in Bavaria. Parentally reported peer relationship problems (‘normal’, ‘borderline’ or ‘abnormal’) were assessed from the Strengths and Difficulties Questionnaire. Overweight and obesity were defined according to age‐ and gender‐specific BMI cut‐off points. Multivariate logistic regression analysis was performed to control potential confounders.

Results:  The prevalence of overweight and obesity was higher among children with ‘borderline’ or ‘abnormal’ peer relationship problems compared to ‘normal’ children. The association of ‘abnormal’ peer relationship problems was still significant in the final logistic regression model for girls [odds ratio (OR) for overweight 2.0; 95% confidence interval (CI): 1.4–3.0; OR for obesity 2.6; 95% CI: 1.3–5.0]. Among boys the adjusted odds ratio were lower and no longer significant.

Conclusion:  The significantly increased prevalence of overweight and obesity among preschool children with peer relationship problems could not be explained by confounding. It seems evident that there is a relevant co‐morbidity of peer relationship problems and obesity in pre‐school children pointing to the need of interventions focusing on both physical as well as psychosocial health.
Is Aquinas a Foundationalist?
Authors: Williams A. N.
Published: August 2009

This essay surveys a range of claims that Aquinas is a foundationalist, along with the rarer position that he is not. It suggests the arguments for holding he is a foundationalist are fundamentally flawed, and that he cannot be considered to hold a foundationalist epistemology, although for reasons more radical than those hitherto suggested. It examines the account of scientia and sacred doctrine in Summa theologiae I.1, with particular attention to its account of metaphor. Sacred doctrine, often taken to be based on scripture, is in fact based on God's self-knowledge, which is mediated by scripture. Aquinas acknowledges that scripture is riddled with figurative language and that metaphor is necessary to sacred doctrine. He emphasises the propensity for human reasoning to go astray, and in virtue of its processes of inference, to be incapable to representing the simplicity of divine knowledge with complete accuracy. Both with respect to its structures of argumentation and the figurative base from which it argues, Aquinas’ account of sacred doctrine is remote from foundationalist accounts of knowledge. Aquinas’ account of sacred doctrine, the most sure of all scientiae, emphasises its fragility and provisionality; its purpose is not to provide certitude, but to provoke reflection.
Living with Betrayal
Authors: Henry Martin
Published: August 2009

This article addresses the idea that, over the centuries, Christianity has survived only by betraying its own uncompromising ideals. It investigates how damaging this interpretation could be for Christianity, and suggests that Christianity's survival might paradoxically be a function of the very phenomenon that seems at first sight to undermine it.
Syndactyly lethal: New mutation with multiple malformations occurring in Sprague Dawley rats
Authors: Fujii Sakiko , Yabe Kaoru , Kimura Yuki , Ito Yukie , Rokukawa Masumi , Furukawa Masatoshi , Ito Kouta , Matsuura Masao , Kiguchi Masao
Published: August 2009

We previously found newborns exhibiting syndactyly of both fore‐ and hindlimbs in a litter from a pair of Sprague Dawley rats. Continuous breeding of the parental animals yielded pups with the same anomaly in following litters, suggesting that the syndactyly was genetic in origin. In the present study, as all the syndactylous pups died on postnatal day 0, we conducted genetic analyses using 30 phenotypically normal female progeny and the sire. The females were subjected to caesarean section on day 20 of gestation and the fetuses were examined for the phenotypes. The results of the mating experiments suggest that the mutant phenotype is caused by a single autosomal recessive gene at a homozygous condition. As homozygous mutants are lethal at the neonatal stage, the mutant gene was named syndactyly lethal, gene symbol syl. The mutant rats have multiple abnormalities, such as syndactyly, micrognathia, fused/absent/small lung lobes, absent kidney and ureter, small spleen, small uterus, fused phalanges, sternoschisis, absent/detached rib, and splitting/fused/absent/small thoracic vertebra, some of which must be the cause of death on postnatal day 0. This mutant is considered to be useful for investigating the mechanisms and/or pathogenesis of syndactyly, as well as the accompanying malformations.
Role of interleukin‐15 in the development of mouse olfactory nerve
Authors: Umehara Tsuyoshi , Udagawa Jun , Takamura Kaoru , Kimura Mitsuhiro , Ishimitsu Ryotaro , Kiyono Hiroshi , Kawauchi Hideyuki , Otani Hiroki
Published: August 2009

Interleukin (IL)‐15 interacts with components of the IL‐2 receptor (R) and exhibits T cell‐stimulating activity similar to that of IL‐2. In addition, IL‐15 is widely expressed in many cell types and tissues, including the central nervous system. We provide evidence of a novel role of IL‐15 in olfactory neurogenesis. Both IL‐15 and IL‐15Rα were expressed in neuronal precursor cells of the developing olfactory epithelium in mice. Adult IL‐15Rα knockout mice had fewer mature olfactory neurons and proliferating cells than wild‐type. Our results suggest that IL‐15 plays an important role in regulating cell proliferation in olfactory neurogenesis.
A single intersubunit salt bridge affects oligomerization and catalytic activity in a bacterial quinone reductase
Authors: Binter Alexandra , Staunig Nicole , Jelesarov Ilian , Lohner Karl , Palfey Bruce A. , Deller Sigrid , Gruber Karl , Macheroux Peter
Published: August 2009

YhdA, a thermostable NADPH:FMN oxidoreductase from Bacillus subtilis, reduces quinones via a ping‐pong bi‐bi mechanism with a pronounced preference for NADPH. The enzyme occurs as a stable tetramer in solution. The two extended dimer surfaces are packed against each other by a 90° rotation of one dimer with respect to the other. This assembly is stabilized by the formation of four salt bridges between K109 and D137 of the neighbouring protomers. To investigate the importance of the ion pair contacts, the K109L and D137L single replacement variants, as well as the K109L/D137L and K109D/D137K double replacement variants, were generated, expressed, purified, crystallized and biochemically characterized. The K109L and D137L variants form dimers instead of tetramers, whereas the K109L/D137L and K109D/D137K variants appear to exist in a dimer–tetramer equilibrium in solution. The crystal structures of the K109L and D137L variants confirm the dimeric state, with the K109L/D137L and K109D/D137K variants adopting a tetrameric assembly. Interestingly, all protein variants show a drastically reduced quinone reductase activity in steady‐state kinetics. Detailed analysis of the two half reactions revealed that the oxidative half reaction is not affected, whereas reduction of the bound FMN cofactor by NADPH is virtually abolished. Inspection of the crystal structures indicates that the side chain of K109 plays a dual role by forming a salt bridge to D137, as well as stabilizing a glycine‐rich loop in the vicinity of the FMN cofactor. In all protein variants, this glycine‐rich loop exhibits a much higher mobility, compared to the wild‐type. This appears to be incompatible with NADPH binding and thus leads to abrogation of flavin reduction.

Structured digital abstract

MINT‐7229866, MINT‐7229874, MINT‐7229885, MINT‐7229894, MINT‐7229905: YhdA (uniprotkb:O07529) and YhdA (uniprotkb:O07529) bind (MI:0407) by blue native page (MI:0276)

MINT‐7229854: YhdA (uniprotkb:O07529) and YhdA (uniprotkb:O07529) bind (MI:0407) by x‐ray crystallography (MI:0114)
Collagen I regulates matrix metalloproteinase‐2 activation in osteosarcoma cells independent of S100A4
Authors: Elenjord Renate , Allen Jasmine B. , Johansen Harald T. , Kildalsen Hanne , Svineng Gunbjørg , Mælandsmo Gunhild M. , Loennechen Thrina , Winberg Jan‐Olof
Published: August 2009

This work investigates the effect of cell–collagen I interactions on the synthesis and activation of MMP‐2, as well as synthesis of MT1‐MMP and TIMP‐1, by using an in vitro model with 3D fibrillar and 2D monomeric collagen. In order to reveal whether the metastasis‐associated protein S100A4 can influence the cell’s response to the two forms of collagen, osteosarcoma cell lines with high and low endogenous levels of S100A4 were used. Attachment of osteosarcoma cells to 3D fibrillar and 2D monomeric collagen resulted in opposite effects on MMP‐2 activation. Attachment to 3D fibrillar collagen decreased activation of proMMP‐2, with a corresponding reduction in MT1‐MMP. By contrast, attachment to monomeric collagen increased the amount of fully active MMP‐2. This was caused by a reduction in TIMP‐1 levels when cells were attached to monomeric 2D collagen. The effect of collagen on proMMP‐2 activation was independent of endogenous S100A4 levels, whereas synthesis of TIMP‐1 was dependent on S100A4. When cells were attached to monomeric collagen, cells with a high level of S100A4 showed a greater reduction in the synthesis of TIMP‐1 than did those with a low level of S100A4. Taken together, this study shows that synthesis and activation of MMP‐2 is affected by interactions between osteosarcoma cells and collagen I in both fibrillar and monomeric form.
Ca2+/calmodulin‐dependent kinase II signalling cascade mediates P2X7 receptor‐dependent inhibition of neuritogenesis in neuroblastoma cells
Authors: Gómez‐Villafuertes Rosa , del Puerto Ana , Díaz‐Hernández Miguel , Bustillo Diego , Díaz‐Hernández Juan I. , Huerta Paula G. , Artalejo Antonio R. , Garrido Juan J. , Miras‐Portugal Ma Teresa
Published: August 2009

ATP, via purinergic P2X receptors, acts as a neurotransmitter and modulator in both the central and peripheral nervous systems, and is also involved in many biological processes, including cell proliferation, differentiation and apoptosis. Previously, we have reported that P2X7 receptor inhibition promotes axonal growth and branching in cultured hippocampal neurons. In this article, we demonstrate that the P2X7 receptor negatively regulates neurite formation in mouse Neuro‐2a neuroblastoma cells through a Ca2+/calmodulin‐dependent kinase II‐related mechanism. Using both molecular and immunocytochemical techniques, we characterized the presence of endogenous P2X1, P2X3, P2X4 and P2X7 subunits in these cells. Of these, the P2X7 receptor was the only functional receptor, as its activation induced intracellular calcium increments similar to those observed in primary neuronal cultures, exhibiting pharmacological properties characteristic of homomeric P2X7 receptors. Patch‐clamp experiments were also conducted to fully demonstrate that ionotropic P2X7 receptors mediate nonselective cation currents in this cell line. Pharmacological inhibition of the P2X7 receptor and its knockdown by small hairpin RNA interference resulted in increased neuritogenesis in cells cultured in low serum‐containing medium, whereas P2X7 overexpression significantly reduced the formation of neurites. Interestingly, P2X7 receptor inhibition also modified the phosphorylation state of focal adhesion kinase, Akt and glycogen synthase kinase 3, protein kinases that participate in the Ca2+/calmodulin‐dependent kinase II signalling cascade and that have been related to neuronal differentiation and axonal growth. Taken together, our results provide the first mechanistic insight into P2X7 receptor‐triggered signalling pathways that regulate neurite formation in neuroblastoma cells.
The miRNA‐192/194 cluster regulates the Period gene family and the circadian clock
Authors: Nagel Remco , Clijsters Linda , Agami Reuven
Published: August 2009

Several biological functions in mammals are regulated in a circadian fashion. The molecular mechanisms orchestrating these circadian rhythms have been unravelled. The biological clock, with its core transcriptional unit Bmal1/CLOCK, is composed of several self‐sustaining feedback loops. In this study, we describe another mechanism impinging on the core components of the circadian clock. Using a forward genetic screen, we identified the miR‐192/194 cluster as a potent inhibitor of the entire Period gene family. In accordance, the exogenous expression of miR‐192/194 leads to an altered circadian rhythm. Thus, our results have uncovered a new mechanism for the control of the circadian clock at the post‐transcriptional level.
Molecular characterization of Arabidopsis thaliana PUF proteins – binding specificity and target candidates
Authors: Francischini Carlos W. , Quaggio Ronaldo B.
Published: August 2009

PUF proteins regulate both stability and translation through sequence‐specific binding to the 3′ UTR of target mRNA transcripts. Binding is mediated by a conserved PUF domain, which contains eight repeats of approximately 36 amino acids each. Found in all eukaryotes, they have been related to several developmental processes. Analysis of the 25 Arabidopsis Pumilio (APUM) proteins presenting PUF repeats reveals that 12 (APUM‐1 to APUM‐12) have a PUF domain with 50–75% similarity to the Drosophila PUF domain. Through three‐hybrid assays, we show that APUM‐1 to APUM‐6 can bind specifically to the Nanos response element sequence recognized by Drosophila Pumilio. Using an Arabidopsis RNA library in a three‐hybrid screening, we were able to identify an APUM‐binding consensus sequence. Computational analysis allowed us to identify the APUM‐binding element within the 3′ UTR in many Arabidopsis transcripts, even in important mRNAs related to shoot stem cell maintenance. We demonstrate that APUM‐1 to APUM‐6 are able to bind specifically to APUM‐binding elements in the 3′ UTR of WUSCHEL, CLAVATA‐1, PINHEAD/ZWILLE and FASCIATA‐2 transcripts. The results obtained in the present study indicate that the APUM proteins may act as regulators in Arabidopsis through an evolutionarily conserved mechanism, which may open up a new approach for investigating mRNA regulation in plants.
Acute exercise reverses TRB3 expression in the skeletal muscle and ameliorates whole body insulin sensitivity in diabetic mice
Authors: Matos A. , Ropelle E. R. , Pauli J. R. , Frederico M. J. S. , De Pinho R. A. , Velloso L. A. , De Souza C. T.
Published: August 2009

Aim:  TRB3 became of major interest in diabetes research when it was shown to interact with and inhibit the activity of Akt. Conversely, physical exercise has been linked to improved glucose homeostasis. Thus, the current study was designed to investigate the effects of acute exercise on TRB3 expression and whole body insulin sensitivity in obese diabetic mice.

Methods:  Male leptin‐deficient (ob/ob) mice swam for two 3‐h‐long bouts, separated by a 45‐min rest period. After the second bout of exercise, food was withdrawn 6 h before antibody analysis. Eight hours after the exercise protocol, the mice were submitted to an insulin tolerance test (ITT). Gastrocnemius muscle samples were evaluated for insulin receptor (IR) and IRS‐1 tyrosine phosphorylation, Akt serine phosphorylation, TRB3/Akt association and membrane GLUT4 expression.

Results:  Western blot analysis showed that TRB3 expression was reduced in the gastrocnemius of leptin‐deficient (ob/ob) mice submitted to exercise when compared with respective ob/ob mice at rest. In parallel, there was an increase in the insulin‐signalling pathway in skeletal muscle from leptin‐deficient mice after exercise. Furthermore, the GLUT4 membrane expression was increased in the muscle after the exercise protocol. Finally, a single session of exercise improved the glucose disappearance (KITT) rate in ob/ob mice.

Conclusion:  Our results demonstrate that acute exercise reverses TRB3 expression and insulin signalling restoration in muscle. Thus, these results provide new insights into the mechanism by which physical activity ameliorates whole body insulin sensitivity in type 2 diabetes.
Chemoreception Scientists Gather under the Florida Sun: The 31st Annual Association for Chemoreception Sciences Meeting
Authors: Wilson Donald A. , Baker Harriet , Brunjes Peter , Gilbertson Timothy A. , Hermer Linda , Hill David L. , Matsunami Hiroaki , Meredith Michael , Mistretta Charlotte M. , Smeets Monique A. M. , Stowers Lisa , Zhuang Hanyi
Published: August 2009

The 31st Annual Association for Chemoreception Sciences (AChemS) met in Sarasota, Florida April 22–26, 2009, attracting approximately 600 registrants and nearly 400 abstracts. In addition to poster and platform presentations, the program offered symposia, special lectures, and various National Institutes of Health (NIH)‐sponsored workshops, including one on computational approaches to olfaction.
Hidden in Plain Sight: The Active Ingredients of Executive Coaching
Authors: McKenna D. Douglas , Davis Sandra L.
Published: August 2009

We propose that I/O psychologists who coach executives have overlooked psychotherapy outcome research as a source of information and ideas that can be used to improve our executive coaching practices. This research, based on thousands of studies and many meta-analyses, has converged on the conclusion that four “active ingredients” account for most of the variance in psychotherapy outcomes. We describe how this literature has identified four primary “active ingredients” that account for most of the variance in psychotherapy outcomes: 1) Client/extratherapeutic factors (40%), 2) The relationship or alliance (30%), 3) Placebo or hope (15%), and 4) Theory and technique (15%). Working on the assumption that psychotherapy and executive coaching are sufficiently similar to justify generalization from one domain to the other, we describe these four active ingredients at length and explore how they may be at work in the executive coaching process. We also suggest that I/O psychologists have training and experience that allows us to leverage some of these active ingredients in our executive coaching (e.g., understanding of client individual differences related to coaching outcomes). But we also have areas of weakness (e.g., building a strong working relationship with an individual client) that may need to be bolstered with additional training and development experiences.
What Is the Active Ingredients Equation for Success in Executive Coaching?
Authors: McKenna D. Douglas , Davis Sandra L.
Published: August 2009

In this response, we address commentator concerns about the generalizability of the active ingredients of psychotherapy to the science and practice of executive coaching. We discuss four ingredient that may make a difference: (a) client characteristics, (b) goals or success criteria, (c) role of the organization, and (d) contextual knowledge of the executive coach. We explore how each of these differences is likely to affect the weighting of the four active ingredients in the equation for predicting executive coaching outcomes. From this analysis, we re-affirm our hypotheses that the active ingredients are generalizable to coaching and hold promise for strengthening research and practice. We conclude by highlighting the efforts of several commentators to extend and deepen our hypotheses to other areas of leadership development.
Growth of a non‐methanotroph on natural gas: ignoring the obvious to focus on the obscure
Authors: Cooley Richard B. , Bottomley Peter J. , Arp Daniel J.
Published: August 2009

Methanotrophs are well known for their ability to grow on methane in natural gas environments; however, these environments also contain low concentrations of longer‐chain‐length gaseous alkanes. This mixture of alkanes poses a problem for organisms that might otherwise grow on alkanes ≥ C2 because methane could inhibit oxidation of growth substrates and lead to an accumulation of toxic C1 metabolites. Here, we have characterized the growth of a C2–C9 alkane‐utilizing bacterium, Thauera butanivorans, in conditions containing high concentrations of methane and small amounts (< 3% of total alkane) of C2–C4. During such growth, methanol accumulates transiently before being consumed in an O2‐dependent process that leads to the formation of a proton gradient and subsequent ATP generation. In contrast, formaldehyde‐dependent O2 consumption is insensitive to uncouplers and does not lead to significant ATP production. This efficient C1 oxidation process that regains much of the energy loss inflicted by oxidizing methane, coupled with an alkane monooxygenase effective at limiting methane oxidation, allows T. butanivorans to grow uninhibited in natural gas environments. Although longer‐chain‐length gaseous alkane‐utilizing organisms have been previously identified to grow in natural gas seepages, the data presented here represent the first detailed characterization of the physiological effects associated with inadvertent methane oxidation by a non‐methanotroph, and suggest the presence of a well‐evolved series of biochemical processes that allow them to grow in natural gas deposits without the need for developing the unique metabolic machinery characteristic of methanotrophs.
Whole‐community genome amplification (WCGA) leads to compositional bias in methane‐oxidizing communities as assessed by pmoA‐based microarray analyses and QPCR
Authors: Bodelier Paul L. E. , Kamst Miranda , Meima‐Franke Marion , Stralis‐Pavese Nancy , Bodrossy Levente
Published: August 2009

Whole‐genome amplification (WGA) using multiple displacement amplification (MDA) has recently been introduced to the field of environmental microbiology. The amplification of single‐cell genomes or whole‐community metagenomes decreases the minimum amount of DNA needed for subsequent molecular community analyses. The resolution of profiling methods of environmental microbial communities will increase substantially by the use of the whole‐community genome amplification (WCGA) procedure, assuming that the original community composition is not affected qualitatively as well as quantitatively. The present study aims to test if WCGA introduces a bias when applied to aerobic proteobacterial methanotrophic communities. For this, first, we subjected samples from freshwater lake sediment to WCGA, and amplified using primers targeting the pmoA gene coding for the α‐subunit of the methane monooxygenase enzyme. Second, we analysed community composition using a diagnostic microarray and quantitative PCR (QPCR) assays. These methods clearly demonstrated that the WCGA amplification introduced a bias. Thus, numbers of γ‐proteobacterial methanotrophs (‘type Ia’) increased significantly while the α‐proteobacterial methanotrophs (‘type II’) were not amplified by the WCGA procedure. It is hypothesized that this bias is caused by the differences in GC content, which may compromise the efficiency of the MDA reaction.
Tensile Strength of Superior Labral Repairs in the Throwing Position
Authors: Alexander Susan , Southgate Dominic F. L , Hill Adam M. , Bull Anthony M. J. , Wallace Andrew L.
Published: August 2009

Background

Type II superior labral (SLAP) tears commonly occur in athletes in the abducted and externally rotated position in the late cocking phase of throwing. This study investigates arthroscopic repairs of SLAP lesions using a knotless polymeric (KINSA) anchor.

Methods

Superficial tissues were dissected from 10 cadaveric shoulders. The glenohumeral capsule was preserved. Type II SLAP tears were created through arthroscopic portals and repaired with two anchors anterior and posterior to the biceps tendon. Glenohumeral joints were then fixed in 60° gleno-humeral abduction in the scapular plane with 1 Nm torque in external rotation to recreate the late cocking phase of the throwing cycle. Specimens were mounted onto an Instron machine and the biceps tendon was loaded until failure.

Results

The mean ultimate peak load was 239 N (SD 101 N). The primary mode of failure was in the tendon substance and 19 out of 20 anchors remained intact in bone.

Conclusion

To our knowledge this is the first study to investigate arthroscopic SLAP repairs in an intact joint in this susceptible position. We conclude that the KINSA anchor can withstand high tensile loads and may be used to treat SLAP tears in high-demand overhead throwing athletes.
Dynamic changes in the direction of blood flow through the ductus arteriosus at birth
Authors: Crossley Kelly J. , Allison Beth J. , Polglase Graeme R. , Morley Colin J. , Davis Peter G. , Hooper Stuart B.
Published: August 2009

Major cardiovascular changes occur at birth, including increased pulmonary blood flow (PBF) and closure of the ductus arteriosus (DA), which acts as a low resistance shunt between the fetal pulmonary and systemic circulations. Although the pressure gradient between these circulations reverses after birth, little is known about DA blood flow changes and whether reverse DA flow contributes to PBF after birth. Our aim was to describe the changes in PBF and DA flow before, during and after the onset of pulmonary ventilation at birth. Flow probes were implanted on the left pulmonary artery (LPA) and DA in preterm fetal sheep (n= 8) ∼3 days before they were delivered and ventilated. Blood flow was measured in the LPA and DA, before and after umbilical cord occlusion (UCO) and for 2 h after ventilation onset. Following UCO, DA flow decreased from 534 ± 57 ml min−1 to 237 ± 29 ml min−1 which reflected a similar reduction in right ventricular output. Within 5 min of ventilation onset, PBF increased from 11 ± 6 ml min−1 to 230 ± 13 ml min−1 whereas DA flow decreased to −172 ± 54 ml min−1; negative values indicate reverse DA flow (left‐to‐right shunting). Reverse flow through the DA contributed up to 50% of total PBF at 30 min and a decrease in this contribution accounted for 71 ± 13% of the time‐related decrease in PBF after birth. DA blood flow is very dynamic after birth and depends upon the pressure gradient between the pulmonary and systemic circulations. Following ventilation, reverse DA flow provided a significant contribution to total PBF after birth.
Asymmetric control of cycle period by the spinal locomotor rhythm generator in the adult cat
Authors: Frigon Alain , Gossard Jean‐Pierre
Published: August 2009

During walking, a change in speed is accomplished by varying the duration of the stance phase, while the swing phase remains relatively invariant. To determine if this asymmetry in the control of locomotor cycles is an inherent property of the spinal central pattern generator (CPG), we recorded episodes of fictive locomotion in decerebrate cats with or without a complete spinal transection (acute or chronic). During fictive locomotion, stance and swing phases typically correspond to extension and flexion phases, respectively. The extension and flexion phases were determined by measuring the duration of extensor and flexor bursts, respectively. In the vast majority of locomotor episodes, cycle period varied more with the extension phase. This was found without phasic sensory feedback, supraspinal structures, pharmacology or sustained stimulation. We conclude that the control of walking speed is governed by an asymmetry within the organization of the spinal CPG, which can be modified by extraneous factors.
High temperature does not alter fatigability in intact mouse skeletal muscle fibres
Authors: Place Nicolas , Yamada Takashi , Zhang Shi‐Jin , Westerblad Håkan , Bruton Joseph D.
Published: August 2009

Intense activation of skeletal muscle results in fatigue development, which involves impaired function of the muscle cells resulting in weaker and slower contractions. Intense muscle activity also results in increased heat production and muscle temperature may rise by up to ∼6°C. Hyperthermia is associated with impaired exercise performance in vivo and recent studies have shown contractile dysfunction and premature fatigue development in easily fatigued muscle fibres stimulated at high temperatures and these defects were attributed to oxidative stress. Here we studied whether fatigue‐resistant soleus fibres stimulated at increased temperature show premature fatigue development and whether increasing the level of oxidative stress accelerates fatigue development. Intact single fibres or small bundles of soleus fibres were fatigued by 600 ms tetani given at 2 s intervals at 37°C and 43°C, which is the highest temperature the muscle would experience in vivo. Tetanic force in the unfatigued state was not significantly different at the two temperatures. With 100 fatiguing tetani, force decreased by ∼15% at both temperatures; the free cytosolic [Ca2+] (assessed with indo‐1) showed a similar ∼10% decrease at both temperatures. The oxidative stress during fatigue at 43°C was increased by application of 10 μm hydrogen peroxide or tert‐butyl hydroperoxide and this did not cause premature fatigue development. In summary, fatigue‐resistant muscle fibres do not display impaired contractility and fatigue resistance at the highest temperature that mammals, including humans, would experience in vivo. Thus, intrinsic defects in fatigue‐resistant muscle fibres cannot explain the decreased physical performance at high temperatures.