bluuebunny/crossref_metadata_2025 huggingface dataset:
Exercise- and hypoxia-induced anaerobic metabolism and recovery: a student laboratory exercise using teleost fish
Authors: Rees B. B. , Boily P. , Williamson L. A. C.
Published: March 2009

Anaerobic metabolism is recruited in vertebrates under conditions of intense exercise or lowered environmental oxygen availability (hypoxia), typically resulting in the accumulation of lactate in blood and tissues. Lactate will be cleared over time after the reoxygenation of tissues, eventually returning to control levels. Here, we present a laboratory exercise developed as part of an upper-level vertebrate physiology class that demonstrates the effects of exercise and hypoxia exposure on blood lactate in fish and the subsequent decrease in lactate during recovery. Typically, the results obtained by students demonstrate that both treatments cause significant increases in blood lactate concentrations (two to three times higher than control values) that decrease back to normal values within 3 h of recovery under normoxia. The procedures described are generally applicable to other fish species and provide an alternative to using humans or other mammalian species to investigate anaerobic metabolism.
Effect of physiological levels of caffeine on Ca2+ handling and fatigue development in Xenopus isolated single myofibers
Authors: Rosser Joelle I. , Walsh Brandon , Hogan Michael C.
Published: March 2009

The purpose of the present study was to determine whether exposure to exogenous physiological concentrations of caffeine influence contractility, Ca2+ handling, and fatigue development in isolated single Xenopus laevis skeletal muscle fibers. After isolation, two identical contractile periods (separated by 60-min rest) were conducted in each single myofiber ( n = 8) at 20°C. During the first contractile period, four fibers were perfused with a noncaffeinated Ringer solution, while the other four fibers were perfused with a caffeinated (70 μM) Ringer solution. The order was reversed for the second contractile period. The single myofibers were stimulated during each contractile period at increasing frequencies (0.16, 0.20, 0.25, 0.33, 0.50, and 1.0 tetanic contractions/s), with each stimulation frequency lasting 2 min until fatigue ensued, defined in this study as a fall in tension development to 66% of maximum. Tension development and free cytosolic [Ca2+] (fura-2 fluorescence spectroscopy) were simultaneously measured. There was no significant difference in the peak force generation, time to fatigue, cytosolic Ca2+ levels, or relaxation times between the noncaffeinated and caffeinated trials. These results demonstrate that physiological levels of caffeine have no significant effect on Xenopus single myofiber contractility, Ca2+ handling, and fatigue development, and suggest that any ergogenic effects of physiological levels of caffeine on muscle performance during contractions of moderate to high intensity are likely related to factors extraneous to the muscle fiber.
Dynamic Causal Modeling of the Response to Frequency Deviants
Authors: Garrido Marta I. , Kilner James M. , Kiebel Stefan J. , Friston Karl J.
Published: March 2009

This article describes the use of dynamic causal modeling to test hypotheses about the genesis of evoked responses. Specifically, we consider the mismatch negativity (MMN), a well-characterized response to deviant sounds and one of the most widely studied evoked responses. There have been several mechanistic accounts of how the MMN might arise. It has been suggested that the MMN results from a comparison between sensory input and a memory trace of previous input, although others have argued that local adaptation, due to stimulus repetition, is sufficient to explain the MMN. Thus the precise mechanisms underlying the generation of the MMN remain unclear. This study tests some biologically plausible spatiotemporal dipole models that rest on changes in extrinsic top-down connections (that enable comparison) and intrinsic changes (that model adaptation). Dynamic causal modeling suggested that responses to deviants are best explained by changes in effective connectivity both within and between cortical sources in a hierarchical network of distributed sources. Our model comparison suggests that both adaptation and memory comparison operate in concert to produce the early (N1 enhancement) and late (MMN) parts of the response to frequency deviants. We consider these mechanisms in the light of predictive coding and hierarchical inference in the brain.
Cuff-induced vascular intima thickening is influenced by titration of the Ace gene in mice
Authors: Lacchini Silvia , Heimann Andrea S. , Evangelista Fabiana S. , Cardoso Leandro , Silva Gustavo J. J. , Krieger José E.
Published: March 2009

We tested the hypothesis that small changes in angiotensin I-converting enzyme (ACE) expression can alter the vascular response to injury. Male mice containing one, two, three, and four copies of the Ace gene with no detectable vascular abnormality or changes in blood pressure were submitted to cuff-induced femoral artery injury. Femoral thickening was higher in 3- and 4-copy mice (42.4 ± 4.3% and 45.7 ± 6.5%, respectively) compared with 1- and 2-copy mice (8.3 ± 1.3% and 8.5 ± 0.9%, respectively). Femoral ACE levels from control and injured vessels were assessed in 1- and 3-copy Ace mice, which represent the extremes of the observed response. ACE vascular activity was higher in 3- vs. 1-copy Ace mice (2.4-fold, P < 0.05) in the control uninjured vessel. Upon injury, ACE activity significantly increased in both groups [2.41-fold and 2.14-fold ( P < 0.05) for 1- and 3-copy groups, respectively] but reached higher levels in 3- vs. 1-copy Ace mice ( P < 0.05). Pharmacological interventions were then used as a counterproof and to indirectly assess the role of angiotensin II (ANG II) on this response. Interestingly, ACE inhibition (enalapril) and ANG II AT1 receptor blocker (losartan) reduced intima thickening in 3-copy mice to 1-copy mouse values ( P < 0.05) while ANG II treatment significantly increased intima thickening in 1-copy mice to 3-copy mouse levels ( P < 0.05). Together, these data indicate that small physiologically relevant changes in ACE, not associated with basal vascular abnormalities or blood pressure levels, do influence the magnitude of cuff-induced neointima thickening in mice.
Toll-like Receptor 9 Activation of Signal Transducer and Activator of Transcription 3 Constrains Its Agonist-Based Immunotherapy
Authors: Kortylewski Marcin , Kujawski Maciej , Herrmann Andreas , Yang Chunmei , Wang Lin , Liu Yong , Salcedo Rosalba , Yu Hua
Published: March 2009

Although toll-like receptor (TLR) agonists, such as CpG, are used as immunotherapeutic agents in clinical trials for cancer and infectious diseases, their effects are limited and the underlying mechanism(s) that restrains CpG efficacy remains obscure. Here, we show that signal transducer and activator of transcription 3 (Stat3) plays a key role in down-modulating immunostimulatory effects of CpG. In the absence of interleukin-6 (IL-6) and IL-10 induction, CpG directly activates Stat3 within minutes through TLR9. Ablating Stat3 in hematopoietic cells results in rapid activation of innate immunity by CpG, with enhanced production of IFN-γ, tumor necrosis factor-α, IL-12, and activation of macrophages, neutrophils, and natural killer cells marked with Stat1 activation. Innate immune responses induced by CpG in mice with a Stat3-ablated hematopoietic system cause potent antitumor effects, leading to eradication of large (>1 cm) B16 melanoma tumors within 72 h. Moreover, ablating Stat3 in myeloid cells increases CpG-induced dendritic cell maturation, T-cell activation, generation of tumor antigen–specific T cells, and long-lasting antitumor immunity. A critical role of Stat3 in mediating immunosuppression by certain cytokines and growth factors in the tumor microenvironment has been recently documented. By demonstrating direct and rapid activation of Stat3 by TLR agonists, we identify a second level of Stat3-mediated immunosuppression. Our results further suggest that targeting Stat3 can drastically improve CpG-based immunotherapeutic approaches. [Cancer Res 2009;69(6):2497–505]
Relationship Between Angiotensin-Converting Enzyme Gene Polymorphism and Body Composition, Functional Performance, and Blood Biomarkers in Advanced Cancer Patients
Authors: Vigano Antonio , Trutschnigg Barbara , Kilgour Robert D. , Hamel Nancy , Hornby Laura , Lucar Enriqueta , Foulkes William , Tremblay Michel L. , Morais José A.
Published: March 2009

Purpose: Nutritional and functional outcome measures have been shown to vary in patients with chronic diseases according to the polymorphic alleles of angiotensin-converting enzyme (ACE), but little is known about the associations between ACE gene polymorphism (ACEGP) and the components of body composition, strength, and selected blood markers in advanced cancer patients (ACP).

Experimental Design: Data were collected from an inception cohort of 172 newly diagnosed ACP with gastrointestinal and non–small cell lung cancer. ACEGP status was defined by the presence of one of the following three combinations of alleles: insertion/insertion, insertion/deletion, and deletion/deletion. Body composition measurements using Dual-energy X-ray Absorptiometry comprised of the following: total fat mass, percent body fat, lean body mass, and appendicular lean mass. Body mass index; handgrip force by Jamar dynamometry; subjective recording of nutrition and performance status as per patient-generated subjective global assessment; cell blood count and differential, serum albumin, ACE, and C-reactive protein were also recorded.

Results: Multiple regression analysis, controlling for gender, age, diagnosis, treatments (radio/chemo), survival, and medication use (ACE inhibitors, anti-inflammatories, statins) revealed the following significant (P ≤ 0.05) relationships in the insertion/deletion compared with insertion/insertion group: higher hemoglobin (Hb; β, 6.39 g/dl; 95% confidence interval, 0.01-12.78), lower total fat mass (−5.78 kg; −11.62 to 0.07), percent body fat (−6.04%; −12.20 to 0.12), and lean body mass (−3.26 kg; −6.78 to 0.26). When comparing the DD to the II group, higher serum ACE (9.10; 1.96-16.25), Hb (6.25 g/dl; −0.63 to 13.12), and handgrip force by Jamar (6.85 lbs; 0.78-12.93) were found.

Conclusion: Of the variables studied, ACEGP seems to be primarily associated with differences in body composition, Hb, and muscle strength in ACP. Further data are needed to determine the clinical effect of ACEGP in cancer cachexia.
A Population Pharmacokinetic Meta-analysis of Sunitinib Malate (SU11248) and Its Primary Metabolite (SU12662) in Healthy Volunteers and Oncology Patients
Authors: Houk Brett E. , Bello Carlo L. , Kang Dongwoo , Amantea Michael
Published: March 2009

Purpose: Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor approved for advanced renal cell carcinoma and imatinib-resistant or imatinib-intolerant gastrointestinal stromal tumor. Following administration, sunitinib is metabolized by cytochrome P450 3A4 to an active metabolite (SU12662). The objective of this analysis was to assess sunitinib and SU12662 pharmacokinetics and to identify covariates that might explain variability in exposure following oral administration.

Experimental Design: Data from 590 subjects (73 volunteers and 517 patients) in 14 studies were analyzed. Plasma concentration-time data were analyzed using nonlinear mixed-effects modeling to estimate population pharmacokinetic parameters, as well as relationships between these parameters and gender, race, age, weight, creatinine clearance, Eastern Cooperative Oncology Group score, and tumor type. Simulations were done to determine the predicted effect of these covariates on exposure.

Results: Separate models were developed for sunitinib and SU12662 (each a two-compartment model with first-order absorption and elimination). Sunitinib parameters were estimated as CL/F, 51.8 L/h and Vd/Fcentral, 2,030 liters. SU12662 parameters were estimated as CL/F, 29.6 L/h and Vd/Fcentral, 3,080 liters. Tumor type (except acute myeloid leukemia), Asian race, gender, body weight, and elevated Eastern Cooperative Oncology Group score described a portion of the variability in CL/F for sunitinib and metabolite; gender and body weight explained some of the variability in Vd/Fcentral for sunitinib and metabolite. Among patients, the predicted changes in sunitinib and metabolite AUC and Cmax as a result of the individual covariates ranged up to 17%.

Conclusion: The magnitude of the predicted changes in exposure with the covariates studied minimizes the necessity for dose adjustment in any of these subpopulations.
Ligand-dependent Notch Signaling Is Involved in Tumor Initiation and Tumor Maintenance in Pancreatic Cancer
Authors: Mullendore Michael E. , Koorstra Jan-Bart , Li Yue-Ming , Offerhaus G. Johan , Fan Xing , Henderson Clark M. , Matsui William , Eberhart Charles G. , Maitra Anirban , Feldmann Georg
Published: March 2009

Purpose: Aberrant activation of the Notch signaling pathway is commonly observed in human pancreatic cancer, although the mechanism(s) for this activation has not been elucidated.

Experimental Design: A panel of 20 human pancreatic cancer cell lines was profiled for the expression of Notch pathway-related ligands, receptors, and target genes. Disruption of intracellular Notch signaling, either genetically by RNA interference targeting NOTCH1 or pharmacologically by means of the γ-secretase inhibitor GSI-18, was used for assessing requirement of Notch signaling in pancreatic cancer initiation and maintenance.

Results: Striking overexpression of Notch ligand transcripts was detectable in the vast majority of pancreatic cancer cell lines, most prominently JAGGED2 (18 of 20 cases, 90%) and DLL4 (10 of 20 cases, 50%). In two cell lines, genomic amplification of the DLL3 locus was observed, mirrored by overexpression of DLL3 transcripts. In contrast, coding region mutations of NOTCH1 or NOTCH2 were not observed. Genetic and pharmacologic inhibition of Notch signaling mitigated anchorage-independent growth in pancreatic cancer cells, confirming that sustained Notch activation is a requirement for pancreatic cancer maintenance. Further, transient pretreatment of pancreatic cancer cells with GSI-18 resulted in depletion in the proportion of tumor-initiating aldehyde dehydrogenase–expressing subpopulation and was associated with inhibition of colony formation in vitro and xenograft engraftment in vivo, underscoring a requirement for the Notch-dependent aldehyde dehydrogenase–expressing cells in pancreatic cancer initiation.

Conclusions: Our studies confirm that Notch activation is almost always ligand dependent in pancreatic cancer, and inhibition of Notch signaling is a promising therapeutic strategy in this malignancy.
Perforation of the Distal End of the Ventriculoperitoneal Shunt into the Bladder with Calculus Formation
Authors: Ramana Murthy K.V. , Jayaram Reddy S. , Prasad D.V.S.R.K.
Published: March 2009

The placement of a ventriculoperitoneal (VP) shunt is the most common form of treatment for hydrocephalus.The distal end of the VP shunt is commonly placed in the peritoneal cavity. Various complications of the distal end of the shunt have been described in the literature.We report an unusual case of perforation of the distal end of the VP shunt into the bladder, with vesical calculus formation.
Activation of Bacillus subtilis Ugd by the BY-Kinase PtkA Proceeds via Phosphorylation of Its Residue Tyrosine 70
Authors: Petranovic Dina , Grangeasse Christophe , Macek Boris , Abdillatef Mohammad , Gueguen-Chaignon Virginie , Nessler Sylvie , Deutscher Josef , Mijakovic Ivan
Published: March 2009

The phosphorylation-dependent activation of bacterial UDP-glucose dehydrogenases by BY-kinases has been previously described in several bacterial model organisms, but the identity of phosphorylated tyrosine(s) and the exact activation mechanism remained unknown. A recent site-specific phosphoproteomic study indicated that tyrosine 70 is phosphorylated in the Bacillus subtilis UDP-glucose dehydrogenase Ugd. In this study we confirm that this tyrosine 70 is indeed the main residue phosphorylated by the cognate BY-kinase PtkA. Homology-based modeling of the Ugd structure using structures from UDP-glucose/GDP-mannose dehydrogenases revealed that this residue is in close proximity to the NAD-binding site. We identified lysine 108 as the second important residue involved in Ugd activation. Enzymatic characterization of the Ugd proteins mutated in residues tyrosine 70 or lysine 108 suggested a phosphorylation-based regulatory mechanism. This study represents the first attempt to understand the activation of a bacterial enzyme by tyrosine phosphorylation at the molecular level.
TRIF, and TRIF-Interacting TLRs Differentially Modulate Several Adenovirus Vector-Induced Immune Responses
Authors: Appledorn D.M. , Patial S. , Godbehere S. , Parameswaran N. , Amalfitano A.
Published: March 2009

The use of Adenovirus (Ad)-based vectors has proven to be a useful platform for the development of gene therapy and vaccine protocols. The immunological mechanisms underlying these properties need to be identified and understood to foster safer, more efficacious use of this important gene transfer platform. Our recent studies have confirmed an important role for MyD88 dependent toll-like receptor (TLR) pathways as mediators of these responses. In this study, we confirm that TLR3, TLR4 and TRIF (TIR-domain-containing adapter-inducing interferon-β) can also have augmentative or inhibitory roles during Ad-induced immune responses. Importantly, our studies revealed that TLR4 acts to suppress several aspects of the Ad-induced innate immune response, a finding not previously reported for this TLR in any model system. In addition, using MyD88 and TRIF double knockout mice, we demonstrate that the MyD88 and TRIF adaptor proteins can play either additive or redundant roles in mediating certain aspects of Ad vector-induced innate and adaptive immune responses. Furthering this complexity, our model system strongly suggests that non-TLR based systems must not only exist, but also have a significant role to play during Ad vector-mediated induction of adaptive immune responses.
Decentralization and the Development of Nationalized Party Systems in New Democracies: Evidence From Latin America
Authors: Harbers Imke
Published: March 2009

The extent to which a party system is nationalized—with nationalization being defined as the degree to which major political parties obtain similar vote shares throughout the national territory—has considerable consequences for political representation, public policy making, and even the survival of democracy. Yet, so far there is little empirical evidence about the conditions that promote or inhibit the development of nationalized party systems in new democracies. Using electoral data from 89 elections in 16 Latin American democracies, this article provides a systematic analysis of the effect of decentralization on party system nationalization. The results show that political decentralization and fiscal decentralization inhibit the development of nationalized party systems, thus suggesting that a trade-off exists between decentralized governance and party system nationalization. These results are robust when controlling for ethnolinguistic fractionalization and characteristics of the electoral system.
New Structuralism and Institutional Change: Federalism Between Centralization and Decentralization
Authors: Erk Jan , Koning Edward
Published: March 2009

This article aims to contribute to the debate on institutional change by introducing social structure as the basis for theorizing about the direction of such change. The empirical context is the long-term trends of federal institutional change in the federations of the industrialized West (Australia, Austria, Belgium, Canada, Germany, Spain, Switzerland, and the United States). It is the authors’ contention that institutions change in order to reach a better fit with the underlying linguistic structure. The direction for institutional change in federal systems with territorially based linguistic heterogeneity is decentralizing, for homogeneous ones the direction is centralizing. The argument is based on the growing importance of language as the provider of democratic space. It is through the less formalized interest group politics that the underlying linguistic base finds its way into influencing the direction of institutional change.
The Ideological Congruence Controversy
Authors: Bingham Powell G.
Published: March 2009

Focusing on the left-right scale as a summary measure of citizens’ and representatives’ preferences, a growing body of literature has used a variety of approaches and data in measuring positions of citizens and representatives. The most recent studies, contrary to previous ones, show no significant difference between ideological congruence in single member district (SMD) and proportional representation (PR) electoral systems. This article examines the major alternative measurement approaches and data sets, finding that recent results are due to differences in time period, not differences in measurement approach. The associations between election rules and ideological congruence are relatively robust to various measurement approaches, as are estimations of the causal processes shaping ideological congruence. The association between election rules and congruence has declined in the past decade, as shown by all three major approaches, due primarily to convergence toward the median of plurality parties in the SMD elections.
Using conversation analysis to study prosodic problems in a child with language impairment
Authors: Samuelsson Christina
Published: March 2009

Prosody carries a lot of information relevant for our understanding of spoken messages. In addition, prosody plays an important role in signalling attitudes and emotions. Prosodic features also constitute an important resource that participants use to achieve mutual understanding in interaction. The aim of this study was to point to possible recurring patterns in the prosodic structure of language testing activities. A further aim was to discuss similarities between English and Swedish in these patterns.

The main findings indicated a systematic use of prosody in the language testing activity. Questions are mainly posed with rising intonation and answers are produced with rising intonation. Evaluations are produced with a final fall in the intonation. There was also some support for the assumption that this pattern occurs within a similar activity involving an English-speaking child and his SLT. The results of the present study showed that analysis of conversation and prosody in its conversational context is useful in order to reveal possible functions of features that would have been overlooked with a more deficit driven perspective.
Language abilities of secondary age pupils at risk of school exclusion: A preliminary report
Authors: Clegg Judy , Stackhouse Joy , Finch Katy , Murphy Claire , Nicholls Shelley
Published: March 2009

In the UK, exclusions from school because of behaviour problems usually occur when other alternatives have proved unsuccessful. There is some evidence to suggest that behaviour problems and resulting school exclusions are associated with language impairment. In older children who are permanently excluded, expressive rather than receptive language impairment is more common and this is associated with increased rates of emotional problems (Ripley and Yuill, 2005). The language abilities of secondary age pupils at risk of permanent school exclusion who are still in mainstream educational provision have not yet been a focus of study. Fifteen pupils attending a mainstream secondary school located in an area of socio-economic deprivation were studied. All the pupils were at risk of permanent exclusion owing to significant behaviour problems. Measures of language and behaviour identified language difficulties in 10 of the 15 pupils, where five of these pupils had significant and severe language difficulties. In contrast, the remaining five pupils showed age-appropriate or typical language abilities. Although differences were identified in language abilities, severe behaviour problems were found in both the pupils with language difficulties and those with age-appropriate language. Mixed receptive-expressive language difficulties were more common than expressive only difficulties but these were not associated with a particular type of behaviour problem. For a high proportion of secondary age pupils at risk of permanent school exclusion, language difficulties are a factor in their behaviour problems and school exclusion. The preliminary findings are discussed with reference to the relationship between language impairment and behaviour problems, the criteria for defining language impairment in this population, the need for further research and potential implications for education and speech and language therapy.
North—South Relations and the Ecological Debt: Asserting a Counter-Hegemonic Discourse
Authors: Rice James
Published: March 2009

We examine position papers by non-governmental organizations (NGOs) arguing for recognition of the ecological debt. We utilize Toulmin's (2003[1958]) model of argument analysis to outline the major claims advanced. The results illustrate the argument is comprised of four interrelated claims: 1) Northern historical development and present disproportionate production and consumption are founded on a socio-ecological subsidy or the underpayment and, at times, explicit looting of the natural resource assets of Southern countries; 2) the Southern external financial debt should be cancelled because it promotes the socio-ecological subsidy; 3) levels of Northern production and consumption are unsustainable over the long term because they are predicated on the North—South socio-ecological subsidy; 4) equity for present and rational obligations to future generations demands Northern countries begin paying back the accrued socio-ecological subsidy, an obligation defined as the ecological debt.
An Energy Harvesting Comparison of Piezoelectric and Ionically Conductive Polymers
Authors: Farinholt Kevin M. , Pedrazas Nicholas A. , Schluneker David M. , Burt David W. , Farrar Charles R.
Published: March 2009

With advances in wireless communications and low power electronics there is an ever increasing need for efficient self-contained power systems. Traditional batteries are often selected for this purpose; however, there are limitations due to finite life-spans and the need to periodically recharge or replace the spent power source. One method to address this issue is the inclusion of an energy harvesting strategy that can scavenge energy from the surrounding environment and convert it into usable electrical energy. Since civil, industrial, and aerospace applications are often plagued with an overabundance of ambient vibrations, electromechanical transducers are often considered a viable choice for energy scavengers. In this study, two classes of transducer are considered: the piezoelectric polymer polyvinylidene fluoride and the ionically conductive ionic polymer transducer. Analytical models are formed for each material assuming axial loading and simulation results are compared with experimental results for each test. Each material is then compared to examine the effectiveness of their mechanoelectric conversion properties.
A Coupled Finite Element—Circuit Simulation Model for Analyzing Piezoelectric Energy Generators
Authors: Elvin Niell G. , Elvin Alex A.
Published: March 2009

A coupled finite element method (FEM) and circuit simulation approach for analyzing piezoelectric energy harvesters is presented. The advantage of the proposed method is that the mechanical analysis of the generator can be done using available FEM packages, while the circuit analysis can be performed using standard circuit simulation software (e.g., SPICE). The electromechanical coupling between the two physical domains is achieved by applying equivalent piezoelectric loads in the mechanical model, and equivalent electrical voltages in the electric model. This approach allows for the modeling of complex mechanical geometries and sophisticated, non-linear circuits. The solutions of two example problems are presented: (1) a beam generator with a resistive load, which is compared to an existing analytical solution, and (2) a plate generator with a non-linear diode bridge circuit. Though relatively easy to implement, the explicit solution technique presented in this article can be computationally expensive for complicated models with long simulation time-histories.
The usefulness of the Revised Psychoeducational Profile for the assessment of preschool children with pervasive developmental disorders
Authors: Portoghese Claudia , Buttiglione Maura , Pavone Francesca , Lozito Vito , De Giacomo Andrea , Martinelli Domenico , Margari Lucia
Published: March 2009

Data from the Psychoeducational Profile—Revised (PEP—R) were analysed in a sample of 46 children, aged from 1.7 to 5.11 years, of whom 21 had autistic disorder (AD) and 25 had pervasive developmental disorder not otherwise specified (PDD-NOS). Analysis with a t-test for independent samples revealed a significant difference ( p < 0.05) between children with AD and those with PDD-NOS on both developmental and behavioural PEP—R scales, supporting the utility of the PEP—R in discriminating between two diagnostic groups. This study emphasizes the effectiveness of the PEP—R as a tool for the early assessment of children with pervasive developmental disorders.
Flail chest: pathophysiology and management
Authors: Qasim Zaffer , Gwinnutt Carl
Published: March 2009

Thoracic trauma is an important cause of morbidity and mortality in the UK, frequently found in drivers of motor vehicles following high-speed accidents. One of the more serious injuries is a flail chest, particularly when there are also underlying pulmonary contusions. For many years the optimal therapeutic regimen for the management of this condition has remained somewhat controversial. More recently, the role of epidural analgesia, the use of non-invasive techniques of ventilation and identification of those who may benefit from surgical stabilisation have been more clearly defined.
Identity, consumption and narratives of socialization
Authors: Shankar Avi , Elliott Richard , Fitchett James A.
Published: March 2009

In this paper we contribute to current debates concerning the relationship between identity and consumption. We use people's past consumption of music, embodied in their old records, as an archive of their identity projects. Using a narrative approach to data collection and drawing on an interpretive orientation influenced by the work of Pierre Bourdieu, we find that the structuring influences that enable and constrain the development of identity emerge in sharper relief. In particular, we suggest that narratives of socialization have an enduring effect on how people `make up' who they want to be. Implications for consumer research theory are discussed.
Brands as relationship facilitators in consumer markets
Authors: Veloutsou Cleopatra
Published: March 2009

This paper examines two types of relationships that consumers form around brands. First there are direct brand and consumer relationships, while the second are the links that a consumer develops with other consumers around brands. This includes brand communities, brand tribes and brand sub-cultures.
BAFF-R promotes cell proliferation and survival through interaction with IKKβ and NF-κB/c-Rel in the nucleus of normal and neoplastic B-lymphoid cells
Authors: Fu Lingchen , Lin-Lee Yen-Chiu , Pham Lan V. , Tamayo Archito T. , Yoshimura Linda C. , Ford Richard J.
Published: March 2009

BLyS and its major receptor BAFF-R have been shown to be critical for development and homeostasis of normal B lymphocytes, and for cell growth and survival of neoplastic B lymphocytes, but the biologic mechanisms of this ligand/receptor-derived intracellular signaling pathway(s) have not been completely defined. We have discovered that the BAFF-R protein was present in the cell nucleus, in addition to its integral presence in the plasma membrane and cytoplasm, in both normal and neoplastic B cells. BAFF-R interacted with histone H3 and IKKβ in the cell nucleus, enhancing histone H3 phosphorylation through IKKβ. Nuclear BAFF-R was also associated with NF-κB/c-Rel and bound to NF-κB targeted promoters including BLyS, CD154, Bcl-xL, IL-8, and Bfl-1/A1, promoting the transcription of these genes. These observations suggested that in addition to activating NF-κB pathways in the plasma membrane, BAFF-R also promotes normal B-cell and B-cell non-Hodgkin lymphoma (NHL-B) survival and proliferation by functioning as a transcriptional regulator through a chromatin remodeling mechanism(s) and NF-κB association. Our studies provide an expanded conceptual view of the BAFF-R signaling, which should contribute a better understanding of the physiologic mechanisms involved in normal B-cell survival and growth, as well as in the pathophysiology of aggressive B-cell malignancies and autoimmune diseases.
Antisense-mediated exon skipping to correct IL-12Rβ1 deficiency in T cells
Authors: van de Vosse Esther , Verhard Els M. , de Paus Roelof A. , Platenburg Gerard J. , van Deutekom Judith C. T. , Aartsma-Rus Annemieke , van Dissel Jaap T.
Published: March 2009

Patients with Mendelian susceptibility to mycobacterial disease have severe, recurrent life-threatening infections with otherwise poorly pathogenic mycobacteria and salmonellae. The extreme susceptibility is the result of genetic defects in the interleukin-12/interferon-γ (IL-12/IFN-γ) pathway. The infections are difficult to treat, and therapeutic options are limited. We explored the feasibility of antisense-mediated exon skipping as therapy for Mendelian susceptibility to mycobacterial disease with cells from a complete IL-12Rβ1−/− patient. Expression constructs were first studied to determine whether IL12RB1 lacking exon 2 encodes a functional protein. The IL-12Rβ1 expression construct lacking exon 2 was expressed on T cells. On IL-12 or IL-23 stimulation, this construct phosphorylated similar amounts of STAT1, STAT3, and STAT4 and induced similar amounts of IFN-γ compared with a normal IL-12Rβ1 construct. Antisense oligonucleotides (AONs) directed at exon 2 resulted in transcripts lacking exon 2 in both controls' and patients' T cells. In IL-12Rβ1−/− cells, skipping of exon 2 led to expression of IL-12Rβ1 on the cell surface and responsiveness to IL-12. We showed that IL12RB1 lacking exon 2 encodes a functional IL-12Rβ1. We demonstrated that T cells can be highly efficiently transduced with AONs and are amenable to antisense-mediated exon skipping. Furthermore, we showed that exon skipping (partly) corrects the IL-12Rβ1 deficiency in patients' cells.
Rapid evolution of mammalian X-linked testis microRNAs
Authors: Guo Xuejiang , Su Bing , Zhou Zuomin , Sha Jiahao
Published: March 2009

Background

MicroRNAs (miRNAs), which are small, non-coding RNAs approximately 21-nucleotides in length, have become a major focus of research in molecular biology. Mammalian miRNAs are proposed to regulate approximately 30% of all protein-coding genes. Previous studies have focused on highly conserved miRNAs, but nonconserved miRNAs represent a potentially important source of novel functionalities during evolution.

Results

An analysis of the chromosome distribution of miRNAs showed higher densities of miRNAs on the X chromosome compared to the average densities on autosomes in all eight mammalian species analyzed. The distribution pattern did not, however, apply well to species beyond mammals. In addition, by comparing orthologous human and mouse miRNAs, we found that X-linked miRNAs had higher substitution rates than autosomal miRNAs. Since the highest proportion of X-linked miRNAs were found in mouse testis, we tested the hypothesis that testis miRNAs are evolving faster on the X chromosome than on autosomes. Mature X-linked testis miRNAs had an average substitution rate between mouse and human that was almost 25-fold higher than mature testis miRNAs on autosomes. In contrast, for mature miRNAs with precursors not expressed in testis, no significant difference in the substitution rate between the X chromosome and autosomes was found. Among mammals, the rapid evolution of X-linked testis miRNAs was also observed in rodents and primates.

Conclusion

The rapid evolution of X-linked testis miRNAs implies possible important male reproductive functions and may contribute to speciation in mammals.
Improvement in right ventricular function during reversibility testing in pulmonary arterial hypertension: a case report
Authors: Huez Sandrine , Vachiéry Jean-Luc , Naeije Robert
Published: March 2009

A right heart catheterization with reversibility testing is recommended for the diagnosis and treatment of pulmonary arterial hypertension. In this 24 years-old woman, the inhalation of 5 μg iloprost transiently decreased mean pulmonary artery pressure from 62 to 36 mmHg and pulmonary vascular resistance from 11.0 to 4.9 Wood units, meeting the criteria of a "positive response". The echocardiographic examination showed normalization of right heart chamber dimensions and of the right ventricular performance (Tei) index. Pulsed tissue Doppler imaging of the right ventricle showed a decrease in the isovolumic relaxation time from 102 to 73 ms, and an increase of the E/A ratio from 0.72 to 1.38, together with marked improvements in mid-apical free wall systolic strain and strain rate. A positive response to reversibility testing of pulmonary arterial hypertension may be associated with quasi normalization of right ventricular function, in spite of still elevated pulmonary artery pressure.
Transgenic up-regulation of alpha-CaMKII in forebrain leads to increased anxiety-like behaviors and aggression
Authors: Hasegawa Shunsuke , Furuichi Takahiro , Yoshida Taro , Endoh Kengo , Kato Kenichi , Sado Megumi , Maeda Ryouta , Kitamoto Aya , Miyao Takahisa , Suzuki Ryosuke , Homma Seiichi , Masushige Shoichi , Kajii Yasushi , Kida Satoshi
Published: March 2009

Background

Previous studies have demonstrated essential roles for alpha-calcium/calmodulin-dependent protein kinase II (alpha-CaMKII) in learning, memory and long-term potentiation (LTP). However, previous studies have also shown that alpha-CaMKII (+/-) heterozygous knockout mice display a dramatic decrease in anxiety-like and fearful behaviors, and an increase in defensive aggression. These findings indicated that alpha-CaMKII is important not only for learning and memory but also for emotional behaviors. In this study, to understand the roles of alpha-CaMKII in emotional behavior, we generated transgenic mice overexpressing alpha-CaMKII in the forebrain and analyzed their behavioral phenotypes.

Results

We generated transgenic mice overexpressing alpha-CaMKII in the forebrain under the control of the alpha-CaMKII promoter. In contrast to alpha-CaMKII (+/-) heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in anxiety-like behaviors in open field, elevated zero maze, light-dark transition and social interaction tests, and a decrease in locomotor activity in their home cages and novel environments; these phenotypes were the opposite to those observed in alpha-CaMKII (+/-) heterozygous knockout mice. In addition, similarly with alpha-CaMKII (+/-) heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in aggression. However, in contrast to the increase in defensive aggression observed in alpha-CaMKII (+/-) heterozygous knockout mice, alpha-CaMKII overexpressing mice display an increase in offensive aggression.

Conclusion

Up-regulation of alpha-CaMKII expression in the forebrain leads to an increase in anxiety-like behaviors and offensive aggression. From the comparisons with previous findings, we suggest that the expression levels of alpha-CaMKII are associated with the state of emotion; the expression level of alpha-CaMKII positively correlates with the anxiety state and strongly affects aggressive behavior.
The mammalian UPR boosts glycoprotein ERAD by suppressing the proteolytic downregulation of ER mannosidase I
Authors: Termine Daniel J. , Moremen Kelley W. , Sifers Richard N.
Published: March 2009

The secretory pathway provides a physical route through which only correctly folded gene products are delivered to the eukaryotic cell surface. The efficiency of endoplasmic reticulum (ER)-associated degradation (ERAD), which orchestrates the clearance of structurally aberrant proteins under basal conditions, is boosted by the unfolded protein response (UPR) as one of several means to relieve ER stress. However, the underlying mechanism that links the two systems in higher eukaryotes has remained elusive. Herein, the results of transient expression, RNAi-mediated knockdown and functional studies demonstrate that the transcriptional elevation of EDEM1 boosts the efficiency of glycoprotein ERAD through the formation of a complex that suppresses the proteolytic downregulation of ER mannosidase I (ERManI). The results of site-directed mutagenesis indicate that this capacity does not require that EDEM1 possess inherent mannosidase activity. A model is proposed in which ERManI, by functioning as a downstream effector target of EDEM1, represents a checkpoint activation paradigm by which the mammalian UPR coordinates the boosting of ERAD.
Mitochondrial diacylglycerol initiates protein-kinase-D1-mediated ROS signaling
Authors: Cowell Catherine F. , Döppler Heike , Yan Irene K. , Hausser Angelika , Umezawa Yoshio , Storz Peter
Published: March 2009

Increases in reactive oxygen species (ROS) have been implicated in age-related diseases, including cancer. The serine/threonine kinase protein kinase D1 (PKD1) is a stress-responsive kinase and sensor for reactive oxygen species, which can initiate cell survival through NF-κB signaling. We have previously shown that in response to ROS, PKD1 is activated at the mitochondria. However, the initial signaling events leading to localization of PKD1 to the mitochondria are unknown. Here, we show that formation of mitochondrial diacylglycerol (DAG) and its binding to PKD1 is the means by which PKD1 is localized to the mitochondria in response to ROS. Interestingly, DAG to which PKD1 is recruited in this pathway is formed downstream of phospholipase D1 (PLD1) and a lipase-inactive PLD1 or inhibition of PLD1 by pharmacological inhibitors blocked PKD1 activation under oxidative stress. To date it has been viewed that monosaturated and saturated DAG formed via PLD1 have no signaling function. However, our data describe a role for PLD1-induced DAG as a competent second messenger at the mitochondria that relays ROS to PKD1-mediated mitochondria-to-nucleus signaling.
In birds, profilin-2a is ubiquitously expressed and contributes to actin-based motility
Authors: Murk Kai , Buchmeier Sabine , Jockusch Brigitte M. , Rothkegel Martin
Published: March 2009

Profilins are small actin-binding proteins expressed in all eukaryotes. They are involved in the regulation of actin filament dynamics and various signalling pathways. The identification of a variety of profilin isoforms led to the assumption that there may be isoform-specific functions. In mammals, profilin-1 (PFN1) is ubiquitously expressed and engaged in the regulation of various motility processes in all cell types. By contrast, profilin-2a (PFN2a) is mainly restricted to neuronal cells and there is evidence that it is involved in neuronal plasticity and membrane trafficking. However, the PFN2a sequence is much better conserved than PFN1 throughout different phyla, indicating that its restricted expression and specialized function in mammals might be unique. Using isoform-specific antibodies, we show that the situation is different in birds. PFN2a is ubiquitously expressed in embryonic and adult chicken tissues at equal and frequently higher amounts than in mammals. Together with PFN1, it is present in cultivated chicken fibroblasts, but differentially localized. Knockdown experiments with miRNA reveal that PFN2a is involved in cell adhesion, spreading and locomotion, and silencing this isoform has pronounced consequences on these processes. Our results indicate profilin isoform expression is differentially regulated among vertebrates.
Oligoastrocytoma of the Brain in a Hooded Crane (Grus monacha)
Authors: Ide T. , Miyoshi N. , Ochiai K. , Yasuda N.
Published: March 2009

A cerebral tumor was identified at necropsy in a mature female hooded crane (Grus monacha). On gross examination, the cut surface of the tumor revealed a soft gelatinous mass. On histologic examination, the tumor was mainly composed of 2 discrete components that resembled oligodendroglioma and astrocytoma. Both components had anaplastic changes, such as pleomorphism, high proliferative activity, microvascular proliferation, and necrosis. The oligodendrogliomatous component showed a honeycomb appearance formed by the accumulation of variably sized neoplastic cells with perinuclear halos and central nuclei. The astrogliomatous component consisted of remarkably pleomorphic cells, including bizarre giant cells. Immunohistochemistry revealed that the oligodendrogliomatous component cells were partially immunoreactive for vimentin and myelin basic protein, and the astrogliomatous component cells were immunoreactive for vimentin, S-100, and glial fibrillary acidic protein. Based on these findings, the tumor was diagnosed as an oligoastrocytoma.
Modeling of Marine Corrosion of Steel Specimens
Authors: Melchers RE
Published: March 2009

Phenomenological modeling of the long term general corrosion of mild and low alloy steel specimens under marine conditions is considered, using weight loss as a function of time. A conceptual model for immersion corrosion, tidal corrosion and atmospheric corrosion under marine conditions is proposed. The model uses accepted theories for short term surface corrosion and employs modern understanding of the action of bacterial colonisation of the surfaces of specimens, including the development of anaerobic conditions. Kinetic, diffusion, nutrient and anaerobic components of the model are identified and mathematical descriptions given. The model is compared to some data available in the literature. Some observations are made about data requirements for further development of models of the type proposed.
Twenty Year Field Study of The Performance of Coatings in Seawater
Authors: Kumar A , Van Blaricum VL , Beitelman A , Boy JH
Published: March 2009

The objectives of this study were to evaluate the long-term performance of various coatings on steel piles in seawater and to investigate non-destructive electrochemical corrosion testing techniques for coating evaluation in the field. Steel H piles which were 20.3 cm x 20.3 cm and 12.2 m long were installed in Buzzards Bay, Cape Cod, Massachusetts. The piles were coated with various coatings such as coal tar epoxy, polyurethane, flame sprayed zinc and aluminum. Several of the piles were left uncoated for baseline comparison. Sacrificial cathodic protection was provided by anodes to some of the bare and coated steel pilings. Corrosion rate measurements using electrochemical polarization resistance and Tafel plots were conducted periodically in the field during the twenty year study. The results of the Cape Cod, MA, corrosion study were compared with a similar study conducted at the La Costa Island, FL. The long-term coating evaluation showed that flame sprayed aluminum with a topcoat sealer performed best at the cooler temperatures in Massachusetts and polyester glass flake was the best performer in Florida. Coal tar epoxy coatings with zinc-rich primers performed well at both of the locations.