bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-Body Responses: Neural Control and Implications for Rehabilitation and Fall Prevention
Authors: Marigold Daniel S. , Misiaszek John E.
Published: February 2009

Humans are one of the unique species that utilize bipedal gait to ambulate in our environment. Despite this fact, coordination of the arms with the legs and the rest of body is essential for many daily activities. As such, whole-body responses have emerged as the preferred strategy following perturbations to balance during both standing and walking. Complex neural circuitry may allow for this coordination through the use of propriospinal pathways linking lumbar and cervical pattern generators in the spinal cord, with supraspinal centers altering this control depending on the context of the situation. Based on these findings, we argue that whole-body reactions may be exploited for rehabilitation purposes. Preliminary results have indicated training programs designed to elicit whole-body responses are effective in reducing falls and improving functional mobility in older adults with and without neurological impairment.
A Role for Preoptic Glutamate in the Regulation of Male Reproductive Behavior
Authors: Dominguez Juan M.
Published: February 2009

Although much progress has been made toward understanding the role of the medial preoptic area (MPOA) in the regulation of male reproductive behaviors, the precise mechanisms responsible for its activation during mating are largely unclear. Several studies implicate glutamate in this response. However, not until recently was there direct evidence supporting this hypothesis. Results obtained using in vivo microdialysis showed that levels of glutamate increased in the MPOA during mating, particularly with ejaculation. Levels then decreased rapidly following ejaculation, during a period of sexual quiescence. The magnitude of this decrease correlated with time spent in quiescence. Additionally, central administration of glutamate uptake inhibitors increased levels of glutamate and facilitated behavior. Glutamate activation of N-methyl-D-aspartate (NMDA) receptors in the MPOA is at least partly responsible for behavioral effects evoked by increase glutamate. This is evidenced by histological analysis of the MPOA, which shows that nearly all cells containing mating-induced Fos also contained NMDA receptors. Mating also increased phosphorylation of NMDA receptors, indicating receptor activation. Finally, bilateral microinjections of NMDA receptor antagonists inhibited copulation. This neurochemical, anatomical, and behavioral evidence points to a key role of preoptic glutamate in the regulation of sexual behavior in males. The implications of these findings are discussed.
Molecular Motors and Synaptic Assembly
Authors: Qian Cai  , Sheng Zu-Hang
Published: February 2009

Proper synaptic function requires the seamless integration of the transport, assembly, and regulation of synaptic components and structures. Inasmuch as the synapse is often distant from the neuronal cell body, newly synthesized synaptic proteins, the precursors of synaptic vesicles, active zone compartments, channels and receptors, and mitochondria, must be transported along lengthy neuronal processes to participate in synaptogenesis. Neuronal transport is mediated by motor proteins that associate with their cargoes via adaptors (or receptors) and that travel along the cytoskeleton network within the neuronal processes. Thus, the identity of membranous protein cargoes and the specificity of motor-cargo interactions are critical for correctly targeting cargoes and properly assembling synapses in developing neurons and in remodeling synapses of mature neurons in response to neuronal activity. In this article, the authors review recent progress in characterizing microtubule- and actin-based motor proteins that are involved in delivering synaptic components and discuss potential mechanisms underlying the formation of motor-receptor-cargo complexes that contribute to synaptogenesis and activity-induced synaptic plasticity.
Psychological Profiles of Internet Sexual Offenders
Authors: Elliott Ian Alexander , Beech Anthony R. , Mandeville-Norden Rebecca , Hayes Elizabeth
Published: February 2009

A sample of 505 Internet sex offenders and 526 contact sex offenders were compared on a range of psychological measures relating to offense-supportive beliefs, empathic concern, interpersonal functioning, and emotional management. Internet offenders could be successfully discriminated from contact offenders on 7 out of 15 measures. Contact offenders were found to have significantly more victim empathy distortions and cognitive distortions than Internet offenders. Internet offenders were found to have significantly higher identification with fictional characters than contact offenders. Further analysis indicated that an increase in scores on scales of fantasy, underassertiveness, and motor impulsivity were predictive of an Internet offense type. An increase in scores of scales of locus of control, perspective taking, empathic concern, overassertiveness, victim empathy distortions, cognitive distortions, and cognitive impulsivity were found to be predictive of a contact offense type. These findings are discussed in the context of the etiology of sexual offending.
Academic Performance in ADHD When Controlled for Comorbid Learning Disorders, Family Income, and Parental Education in Brazil
Authors: Carmine Pastura Giuseppe Mario , Mattos Paulo , Campos Araújo Alexandra Prufer de Queiroz
Published: February 2009

Objective: Scholastic achievement in a nonclinical sample of ADHD children and adolescents was evaluated taking into consideration variables such as comorbid learning disorders, family income, and parental education which may also be associated with poor academic performance. Method: After screening for ADHD in 396 students, the authors compared academic performance of 26 ADHD individuals and 31 controls paired for gender, age, and intelligence level considering both mathematics and Portuguese language scores. Learning disorders were investigated and the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV ) criteria were met using structured interviews. Results: The prevalence of academic underachievement was 2.98 times higher in students with ADHD, the most frequent subtype being predominantly inattentive. Parental educational level, family income, and comorbid learning disorders could not explain the discrepancies between ADHD students and controls. Conclusions: ADHD seems to be associated with poor academic performance even in the absence of comorbid learning disorders, lower family income, and parental educational level. ( J. of Att. Dis. 2009; 12(5) 469-473)
On the Computational Rendition of Reality: Artefacts and Human Agency
Authors: Kallinikos Jannis
Published: February 2009

The paper seeks to lay open the computational logic by which reality is rendered as information. Computation is claimed to involve a drift away from the palpable and extendible character of things, a trend that both continues and breaks with the prevailing strategies of technological mediation in industrialism and modernity. Computation entails the relentless analytic reduction of the composite character and complexion of the world. Reality is meticulously dissolved and regained after a long analytic retreat and technological reconstruction. The outcome of this analytic strategy is that processes taking place at the human-technology interface are sustained by an elaborate vertical stratification, entailing a variety of other programmes and systems that reach down from the level of the interface to machine language and the mechanics of binary parsing. The deepening involvement of computation in instrumental settings thus reframes the perceptive and action modalities by which human agents confront the world. This way, a coherent set of techniques for building up reality is established accompanied by a new model of human agency that increasingly takes the form of a combinatoria of data and information items, remaking the shape of things out of the digital fragments produced by computation.
Gendering Finance: Masculinities and Hierarchies at the Stockholm Stock Exchange
Authors: Blomberg Jesper
Published: February 2009

Based on survey data, interviews and observations, this paper examines the division of labour between men and women in stock-brokerage firms active on the Stockholm Stock Exchange. Starting off with a simplistic view of internalized (sex) roles and normative order, according to which men are valued higher than women in the world of finance, the analysis gradually shifts towards a focus on reflexive actors and local interaction. The analysis ends up proposing that this specific gender regime is best interpreted as produced by situated face-to-face encounters between foremost male analysts and male brokers. These two categories of men have unstable and contradictory status relations to each other, which threaten the identity, community and status of the brokers. The encounters between male brokers and male analysts produce a rather sexist and female-discriminating discourse and at least two different versions of masculinity.
Exploring the Edges of Theory-Practice Gap: Epistemic Cultures in Strategy-Tool Development and Use
Authors: Moisander Johanna , Stenfors Sari
Published: February 2009

This paper takes a strategy-as-practice perspective on the study of strategy tools and the theory-practice gap in strategic management research. Based on a case study, the paper argues that differences in epistemic culture may complicate communication and co-operation between academics and practitioners. These differences may also result in management scholars producing knowledge and strategy tools that lack practical pertinence for corporate actors, particularly in the context of modernist management scholars and contemporary post-bureaucratic knowledge organizations (PBOs). In PBOs, where flexibility, participative management style and consensus building dialogue are emphasized, modernist strategy tools designed for rational problem solving by individual decision-makers may be inadequate. In PBOs, practical strategy work calls for tools that support collective knowledge production, promote dialogue and trust, and function as learning tools. Overall, the paper concludes that the development of strategy tools that actually support practical strategizing calls for a more social model of knowledge and strategy work.
Mobile phone text messaging to promote healthy behaviors and weight loss maintenance: a feasibility study
Authors: Gerber Ben S. , Stolley Melinda R. , Thompson Allison L. , Sharp Lisa K. , Fitzgibbon Marian L.
Published: February 2009

There is a need to investigate newer strategies pertaining to the maintenance of healthy behaviors and weight. We investigated the feasibility of mobile phone text messaging to enable ongoing communication with African-American women participating in a weight management program. Ninety-five African-American women participated in this pilot study and received regularly scheduled text messages. Forty-two of these women chose to create 165 personal text messages that included tips on healthy eating and physical activity, as well as reminders to drink water and expressions of encouragement. A commercially available client-based application transmitted these personal messages and general health messages at least three times per week. The software transmitted over 4500 text messages during the first 4 months with 114 returned as undeliverable. Participants expressed generally positive attitudes toward incoming text messages, with only one participant declining to continue after enrollment. This study demonstrated early feasibility and acceptability of text messaging as a method for promoting healthy behaviors for weight maintenance.
Mechanisms behind GLP-1 induced weight loss
Authors: Larsen Philip J
Published: February 2009

Endogenous glucagon-like peptide-1 (GLP-1) is an incretin hormone that plays an important role in maintaining pancreatic function as well as caloric intake. Since the advent of GLP-1 receptor agonists resistant to dipeptidyl peptidase-4 (DPP-4) (degradation, it has become clear that their chronic use promotes negative energy balance. With regard to their effects on body weight, the principal action of GLP-1 agonists is mediated via their inhibition of eating. In searching for the underlying mechanism of GLP-1 receptor agonist-induced anorexic effect, scientists have discovered pathways in the central nervous system, as well as in the periphery. This review describes emerging knowledge of a peripheral endocrine GLP-1 system mediating its activity through a central ascending GLP-1 pathway and targeting hypothalamic sites involved in the regulation of energy homeostasis. Thus peripheral and central GLP-1 sensitive pathways appear to be organised to co-operatively help control food intake and body weight.Br J Diabetes Vasc Dis 2008;8 (Suppl 2): S34—S41
Increasing Fresh Fruit and Vegetable Availability in a Low-Income Neighborhood Convenience Store: A Pilot Study
Authors: Jetter Karen M. , Cassady Diana L.
Published: February 2009

Changing the food environment in low-income communities may be an effective way to increase the consumption of fruits and vegetables by low-income consumers. This study examines the impacts of a pilot study that increases the availability of fresh produce in a convenience store in a low-income neighborhood not served by a supermarket. Two hypotheses based on theories of technology adoption are tested regarding the lack of fresh produce in low-income neighborhood stores: the first is that high fixed costs present a barrier for store owners in developing produce sections; the second is that there is insufficient consumer demand to cover the variable costs of a fresh produce section. The impacts of changing the food environment on store owners and the consumer response to environmental change are measured through weekly inventories of fresh produce. The results show that fixed costs are one barrier for store owners and that although the consumer response is sufficient to cover the direct costs of operating the produce case, it is not enough to cover variable management costs. Consequently, alternative management paradigms or venues may offer a better method to meet the demand for fresh produce by low-income consumers to promote better health through healthier diets in low-income communities.
Developing Core Sets for Persons With Traumatic Brain Injury Based on the International Classification of Functioning, Disability, and Health
Authors: Bernabeu Montserrat , Laxe Sara , Lopez Raquel , Stucki Gerold , Ward Anthony , Barnes Michael , Kostanjsek Nenad , Reed Geoffrey , Tate Robyn , Whyte John , Zasler Nathan , Cieza Alarcos
Published: February 2009

The authors outline the process for developing the International Classification of Functioning, Disability, and Health (ICF) Core Sets for traumatic brain injury (TBI). ICF Core Sets are selections of categories of the ICF that identify relevant categories of patients affected by specific diseases. Comprehensive and brief ICF Core Sets for TBI should become useful for clinical practice and for research. The final definition of the ICF Core Sets for TBI will be determined at an ICF Core Sets Consensus Conference, which will integrate evidence from preliminary studies. The development of ICF Core Sets is an inclusive and open process and rehabilitation professionals are invited to participate.
Redistribution and Financing Schools in England under Labour
Authors: West Anne
Published: February 2009

This article explores the policy changes made by the Labour government to the recurrent funding of school-based education in England, focusing in particular on the allocation of resources to meet the needs of disadvantaged pupils. Expenditure on education and, in particular, on schools has increased since 1997. However, while there have been two major changes to the way in which government allocates resources to local authorities (LAs) and a new requirement for LAs to include a deprivation factor in their funding formulae for schools, the evidence indicates that resources are being allocated to schools in a less redistributive manner than they are being allocated by central government to LAs. To address this issue, the government could require a minimum proportion of funding to be allocated to schools on the basis of disadvantage; however, politically this would be problematic in the absence of additional resources as it would mean cuts being made by LAs elsewhere in the education budget. And whilst there is now some information about the level of funding allocated to meet the needs of disadvantaged pupils, there is a paucity of information about how these resources are actually used within schools.
Globalization and its Impact on Education with Specific Reference to Education in South Africa
Authors: Moloi K.C. , Gravett S.J. , Petersen N.F.
Published: February 2009

As globalization of the world economy continues unabated, a parallel growth of globalization of knowledge is also taking place. This latter trend is little affected by the boundaries between developed and less developed countries and is having a particular impact on trends in education. This article looks at the impact of globalization within the context of education in South Africa. It focuses on different perspectives of globalization and identifies key factors that may have an impact on education in South Africa. Finally, it argues that in order to respond to the dangers of marginalization posed by globalization it will be crucial to form, and be part of, new alliances and networks. These will both provide opportunities for sharing knowledge and skills and also build economic strength.
Effect of ZnO coating of whiskers on thermal expansion properties of aluminium borate whisker reinforced aluminium composites
Authors: Yue H. Y. , Wang L. D. , Fei W. D.
Published: February 2009

The pure aluminium composites reinforced by ZnO coated aluminium borate whiskers were fabricated by squeeze casting. The microstructure of the composite was observed using an optical microscope and the thermal expansion behaviours of the composites were investigated in the range from 50 to 400°C. In addition, the effects of heat treatment and thermal cycling on the thermal expansion behaviours of the composite were also investigated. The results show that the coefficient of thermal expansion of as cast composites decreases with the ZnO coating content increasing. However, heat treatment time and thermal cycling lead to an increase in the CTE of the composite.
Study of fractional softening of AZ31 magnesium alloy under multistage hot deformation
Authors: Shamsi M. , Sanjari M. , Hanzaki A. Zarei
Published: February 2009

In the present study flow softening behaviour of AZ31 magnesium alloy was investigated by double hit compression tests in the temperature range 250–400°C and strain rate range 10–3–10–1 s–1. The tests were conducted with delay times varying 4–250 s after achieving the critical strain ϵc in each deformation condition. It has been found that static restoration processes (recovery and recrystallisation) were intensely depended on strain rate and deformation temperature. Fractional softening values increased with increasing strain rate and deformation temperature. Accordingly the softening curves were divided into three regions. The softening in the short interpass times was attributed to the occurrence of static recovery and followed by static recrystallisation and grain growth as dominant softening mechanisms for the second and third regions respectively. In addition static recrystallisation kinetics was interpreted by Avrami equation. Analysis of the results indicated that Avrami constant was changed by varying temperature.
Interface characterisation of diffusion bonded Ti–6Al–4V alloy and austenitic stainless steel couple
Authors: Kurt B. , Orhan N. , Kaya M.
Published: February 2009

In this study, the Ti–6Al–4V alloy was diffusion bonded to austenitic stainless steel at temperatures of 820, 885, 930 and 980°C, under a pressure of 5 MPa for 30 min. The effect of temperature on interface formations and microstructure was investigated using a scanning electron microscope (SEM), energy dispersive spectrograph (EDS) microanalyses, X-ray diffraction and shear strength of bonded specimens. The results showed that intermetallic phases and σ-phase formed in the interface region.
Poly(ethylene terephalate) prepolymer graft modification of nano-TiO2 and its effect on mechanical property of polycarbonate nanocomposites
Authors: Li L. , Shi L.-Y. , Zhang Y. , Cao S.-M. , Feng X.
Published: February 2009

Nano-TiO2 particles were modified by the poly(ethylene terephalate) prepolymer (pre-PET) via polycondensation. Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy results showed that pre-PET was successfully grafted on the surface of the nano-TiO2 particles. Thermogravimetric analysis results indicated that the grafting efficiency depended on the vacuum degree. Compared to the original nano-TiO2, the grafted nano-TiO2 had better compatibility with the polycarbonate (PC) matrix and could be dispersed more homogeneously in PC. Hence, interfacial adhesion between TiO2 and PC was enhanced. The mechanical properties of the resultant PC/nano-TiO2 composites like tensile strength and notched impact strength were greatly improved. Calculated respectively from tensile yield stress PC/nano-TiO2 composites, the interfacial interaction parameter B was employed to quantitatively characterise the effective interfacial interaction between the nano-TiO2 and PC matrix. It demonstrated that the nano-TiO2 grafted with pre-PET had stronger effective interfacial interaction with PC matrix than original nano-TiO2.
Plasma surface treatment to improve fracture toughness of aluminium/aluminium foam composites
Authors: Chung H. J. , Rhee K. Y. , Lee Y.-H. , Kim H.
Published: February 2009

In the present study, the effect of a plasma treatment using nitrogen gas on the fracture characteristics of adhesively bonded aluminium foam/aluminium composites was investigated. Fracture tests were performed on three types of single lap shear test samples: untreated aluminium foam/aluminium (case 1), plasma treated aluminium foam/untreated aluminium (case 2) and untreated aluminium foam/plasma treated aluminium (case 3). Fracture toughness was determined by the work factor method. Results showed that the plasma treatment of aluminium foam and aluminium materials using nitrogen gas has a positive effect on the fracture toughness of aluminium foam/aluminium composites. Specifically, the fracture toughness values in cases 2 and 3 improved by about 150 and 200% respectively compared with those in case 1. The fracture surface analysis showed that an adhesive fracture occurred in both cases 1 and 2, whereas a cohesive failure occurred for case 3. The occurrence of cohesive fracture was a result of increased hydrophilicity on the aluminium surface caused by the plasma treatment, which led to a greater adhesion of epoxy to the surface.
Impaired neutrophil extracellular trap (NET) formation: a novel innate immune deficiency of human neonates
Authors: Yost Christian C. , Cody Mark J. , Harris Estelle S. , Thornton Nathan L. , McInturff Alison M. , Martinez Mark L. , Chandler Nancy B. , Rodesch Christopher K. , Albertine Kurt H. , Petti Cathy A. , Weyrich Andrew S. , Zimmerman Guy A.
Published: February 2009

Neutrophils are highly specialized innate effector cells that have evolved for killing of pathogens. Human neonates have a common multifactorial syndrome of neutrophil dysfunction that is incompletely characterized and contributes to sepsis and other severe infectious complications. We identified a novel defect in the antibacterial defenses of neonates: inability to form neutrophil extracellular traps (NETs). NETs are lattices of extracellular DNA, chromatin, and antibacterial proteins that mediate extracellular killing of microorganisms and are thought to form via a unique death pathway signaled by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase–generated reactive oxygen species (ROS). We found that neutrophils from term and preterm infants fail to form NETs when activated by inflammatory agonists—in contrast to leukocytes from healthy adults. The deficiency in NET formation is paralleled by a previously unrecognized deficit in extracellular bacterial killing. Generation of ROSs did not complement the defect in NET formation by neonatal neutrophils, as it did in adult cells with inactivated NADPH oxidase, demonstrating that ROSs are necessary but not sufficient signaling intermediaries and identifying a deficiency in linked or downstream pathways in neonatal leukocytes. Impaired NET formation may be a critical facet of a common developmental immunodeficiency that predisposes newborn infants to infection.
A novel variant on chromosome 7q22.3 associated with mean platelet volume, counts, and function
Authors: Soranzo Nicole , Rendon Augusto , Gieger Christian , Jones Chris I. , Watkins Nicholas A. , Menzel Stephan , Döring Angela , Stephens Jonathan , Prokisch Holger , Erber Wendy , Potter Simon C. , Bray Sarah L. , Burns Philippa , Jolley Jennifer , Falchi Mario , Kühnel Brigitte , Erdmann Jeanette , Schunkert Heribert , Samani Nilesh J. , Illig Thomas , Garner Stephen F. , Rankin Angela , Meisinger Christa , Bradley John R. , Thein Swee Lay , Goodall Alison H. , Spector Tim D. , Deloukas Panos , Ouwehand Willem H.
Published: February 2009

Mean platelet volume (MPV) and platelet count (PLT) are highly heritable and tightly regulated traits. We performed a genome-wide association study for MPV and identified one SNP, rs342293, as having highly significant and reproducible association with MPV (per-G allele effect 0.016 ± 0.001 log fL; P < 1.08 × 10−24) and PLT (per-G effect −4.55 ± 0.80 109/L; P < 7.19 × 10−8) in 8586 healthy subjects. Whole-genome expression analysis in the 1-MB region showed a significant association with platelet transcript levels for PIK3CG (n = 35; P = .047). The G allele at rs342293 was also associated with decreased binding of annexin V to platelets activated with collagen-related peptide (n = 84; P = .003). The region 7q22.3 identifies the first QTL influencing platelet volume, counts, and function in healthy subjects. Notably, the association signal maps to a chromosome region implicated in myeloid malignancies, indicating this site as an important regulatory site for hematopoiesis. The identification of loci regulating MPV by this and other studies will increase our insight in the processes of megakaryopoiesis and proplatelet formation, and it may aid the identification of genes that are somatically mutated in essential thrombocytosis.
Chronological expression ofCiliated Bronchial Epithelium 1during pulmonary development
Authors: Haitchi H. M. , Yoshisue H. , Ribbene A. , Wilson S. J. , Holloway J. W. , Bucchieri F. , Hanley N. A. , Wilson D. I. , Zummo G. , Holgate S. T. , Davies D. E.
Published: February 2009

Ciliated Bronchial Epithelium(CBE)1is a novel gene, which is expressed in ciliated cells. As cilia are important during embryogenesis, the present authors characterised the murine homologue ofCBE1(Cbe1) and compared its temporal expression during murine and human lung development.

Cbe1cDNA was cloned and characterised using sequencing, standard PCR and Western blotting. Mouse and human embryonic/fetal lungs (HELs) were harvested for mRNA analysis and protein localisationin vivoandin vitrousing RT-PCR and immunohistochemistry.

The Cbe1 amino acid sequence was >75% identical with CBE1 and its alternative splicing and tissue distribution were highly conserved. Pulmonary expression ofCbe1mRNA was increased at embryonic day (E)16, 1 day later thanFoxj1, which is consistent with a role in ciliogenesis. In HELs,CBE1mRNA was detectable at 8–9 weeks post-conception and increased in explant culture. CBE1 protein expression was weak at 10 weeks post-conception but strong at 12.3 weeks post-conception, in parallel with cilia formation. Additionally,Cbe1mRNA was expressed at E11 (4–5 weeks post-conception in HELs) in the absence ofFoxj1, implying a distinct role in early development.

Chronological regulation ofCBE1/Cbe1expression during pulmonary differentiation suggests involvement in ciliogenesis, with an additional role during early lung development.
Iloprost for pulmonary vasodilator testing in idiopathic pulmonary arterial hypertension
Authors: Jing Z-C. , Jiang X. , Han Z-Y. , Xu X-Q. , Wang Y. , Wu Y. , Lv H. , Ma C-R. , Yang Y-J. , Pu J-L.
Published: February 2009

The aim of this study was to confirm the utility of aerosolised iloprost for identifying long-term responders to calcium channel blockers (CCBs) in patients with idiopathic pulmonary arterial hypertension (IPAH).

While undergoing right heart catheterisation, 74 patients with IPAH sequentially received incremental infusions of adenosine and aerosolised iloprost. The effects of the two vasodilators on haemodynamic parameters were recorded. All acute responders identified by aerosolised iloprost were subsequently treated with high doses of a CCB and were re-evaluated after 12 months.

Both adenosine and iloprost produced significant decreases in mean pulmonary arterial pressure and pulmonary vascular resistance, and significant increases in cardiac index. Adverse effects were experienced by 35 out of the 74 patients with adenosine, but by only two with iloprost. Aerosolised iloprost identified more acute responders than infused adenosine (10versuseight, respectively) according to the criteria recommended in recent consensus guidelines. Nine responders identified by iloprost were followed-up after 12 months of high-dose CCB therapy. Five had normal or near-normal haemodynamics and a World Health Organization functional classification of I or II after 12 months.

Aerosolised iloprost is an appropriate new agent to identify long-term responders to CCBs in patients with IPAH. It is as effective in this regard as infused adenosine but is better tolerated.
Evaluating the association of common APOA2variants with type 2 diabetes
Authors: Duesing Konsta , Charpentier Guillaume , Marre Michel , Tichet Jean , Hercberg Serge , Balkau Beverley , Froguel Philippe , Gibson Fernando
Published: February 2009

Background

APOA2 is a positional and biological candidate gene for type 2 diabetes at the chromosome 1q21-q24 susceptibility locus. The aim of this study was to examine if HapMap phase II tag SNPs in APOA2 are associated with type 2 diabetes and quantitative traits in French Caucasian subjects.

Methods

We genotyped the three HapMap phase II tagging SNPs (rs6413453, rs5085 and rs5082) required to capture the common variation spanning the APOA2 locus in our type 2 diabetes case-control cohort comprising 3,093 French Caucasian subjects. The association between these variants and quantitative traits was also examined in the normoglycaemic adults of the control cohort. In addition, meta-analysis of publicly available whole genome association data was performed.

Results

None of the APOA2 tag SNPs were associated with type 2 diabetes in the French Caucasian case-control cohort (rs6413453, P = 0.619; rs5085, P = 0.245; rs5082, P = 0.591). However, rs5082 was marginally associated with total cholesterol levels (P = 0.026) and waist-to-hip ratio (P = 0.029). The meta-analysis of data from 12,387 subjects confirmed our finding that common variation at the APOA2 locus is not associated with type 2 diabetes.

Conclusion

The available data does not support a role for common variants in APOA2 on type 2 diabetes susceptibility or related quantitative traits in Northern Europeans.
Export of recombinant proteins in Escherichia coli using ABC transporter with an attached lipase ABC transporter recognition domain (LARD)
Authors: Chung Chan Woo , You Jinsun , Kim Kyeongyeon , Moon Yuseok , Kim Hoeon , Ahn Jung Hoon
Published: February 2009

Background

ATP binding cassette (ABC) transporter secretes the protein through inner and outer membranes simultaneously in gram negative bacteria. Thermostable lipase (TliA) of Pseudomonas fluorescens SIK W1 is secreted through the ABC transporter. TliA has four glycine-rich repeats (GGXGXD) in its C-terminus, which appear in many ABC transporter-secreted proteins. From a homology model of TliA derived from the structure of P. aeruginosa alkaline protease (AprA), lipase ABC transporter domains (LARDs) were designed for the secretion of fusion proteins.

Results

The LARDs included four glycine-rich repeats comprising a β-roll structure, and were added to the C-terminus of test proteins. Either Pro-Gly linker or Factor Xa site was added between fusion proteins and LARDs. We attached different length of LARDs such as LARD0, LARD1 or whole TliA (the longest LARD) to three types of proteins; green fluorescent protein (GFP), epidermal growth factor (EGF) and cytoplasmic transduction peptide (CTP). These fusion proteins were expressed in Escherichia coli together with ABC transporter of either P. fluorescens or Erwinia chrysanthemi. Export of fusion proteins with the whole TliA through the ABC transporter was evident on the basis of lipase enzymatic activity. Upon supplementation of E. coli with ABC transporter, GFP-LARDs and EGF-LARDs were excreted into the culture supernatant.

Conclusion

The LARDs or whole TliA were attached to C-termini of model proteins and enabled the export of the model proteins such as GFP and EGF in E. coli supplemented with ABC transporter. These results open the possibility for the extracellular production of recombinant proteins in Pseudomonas using LARDs or TliA as a C-terminal signal sequence.
Is peer review useful in assessing research proposals in Indigenous health? A case study
Authors: Street Jackie , Baum Fran , Anderson Ian PS
Published: February 2009

Background

There has been considerable examination and critique of traditional (academic) peer review processes in quality assessment of grant applications. At the same time, the use of traditional research processes in Indigenous research has been questioned. Many grant funding organisations have changed the composition of their peer review panels to reflect these concerns but the question remains do these reforms go far enough? In this project we asked people working in areas associated with Aboriginal health research in a number of capacities, their views on the use of peer review in assessing Indigenous research proposals.

Methods

In semi-structured interviews we asked 18 individuals associated with an Australian Indigenous research funding organisation to reflect on their experience with peer review in quality assessment of grant applications. We also invited input from a steering group drawn from a variety of organisations involved in Aboriginal research throughout Australia and directly consulted with three Aboriginal-controlled health organisations.

Results

There was consensus amongst all participants that traditional academic peer review is inappropriate for quality assessment in Indigenous research. Many expressed the view that using a competitive grant review system in Aboriginal health was counterintuitive, since good research transfer is based on effective collaboration. The consensus within the group favoured a system which built research in a collaborative manner incorporating a variety of different stakeholders in the process. In this system, one-off peer review was still seen as valuable in the form of a "critical friend" who provided advice as to how to improve the research proposal.

Conclusion

Peer review in the traditional mould should be recognised as inappropriate in Aboriginal research. Building research projects relevant to policy and practice in Indigenous health may require a shift to a new way of selecting, funding and conducting research.
APOBEC3G induces a hypermutation gradient: purifying selection at multiple steps during HIV-1 replication results in levels of G-to-A mutations that are high in DNA, intermediate in cellular viral RNA, and low in virion RNA
Authors: Russell Rebecca A , Moore Michael D , Hu Wei-Shau , Pathak Vinay K
Published: February 2009

Background

Naturally occurring Vif variants that are unable to inhibit the host restriction factor APOBEC3G (A3G) have been isolated from infected individuals. A3G can potentially induce G-to-A hypermutation in these viruses, and hypermutation could contribute to genetic variation in HIV-1 populations through recombination between hypermutant and wild-type genomes. Thus, hypermutation could contribute to the generation of immune escape and drug resistant variants, but the genetic contribution of hypermutation to the viral evolutionary potential is poorly understood. In addition, the mechanisms by which these viruses persist in the host despite the presence of A3G remain unknown.

Results

To address these questions, we generated a replication-competent HIV-1 Vif mutant in which the A3G-binding residues of Vif, Y40RHHY44, were substituted with five alanines. As expected, the mutant was severely defective in an A3G-expressing T cell line and exhibited a significant delay in replication kinetics. Analysis of viral DNA showed the expected high level of G-to-A hypermutation; however, we found substantially reduced levels of G-to-A hypermutation in intracellular viral RNA (cRNA), and the levels of G-to-A mutations in virion RNA (vRNA) were even further reduced. The frequencies of hypermutation in DNA, cRNA, and vRNA were 0.73%, 0.12%, and 0.05% of the nucleotides sequenced, indicating a gradient of hypermutation. Additionally, genomes containing start codon mutations and early termination codons within gag were isolated from the vRNA.

Conclusion

These results suggest that sublethal levels of hypermutation coupled with purifying selection at multiple steps during the early phase of viral replication lead to the packaging of largely unmutated genomes, providing a mechanism by which mutant Vif variants can persist in infected individuals. The persistence of genomes containing mutated gag genes despite this selection pressure indicates that dual infection and complementation can result in the packaging of hypermutated genomes which, through recombination with wild-type genomes, could increase viral genetic variation and contribute to evolution.
MODY-like diabetes associated with an apparently balanced translocation: possible involvement of MPP7 gene and cell polarity in the pathogenesis of diabetes
Authors: Bhoj Elizabeth J , Romeo Stefano , Baroni Marco G , Bartov Guy , Schultz Roger A , Zinn Andrew R
Published: February 2009

Background

Characterization of disease-associated balanced translocations has led to the discovery of genes responsible for many disorders, including syndromes that include various forms of diabetes mellitus. We studied a man with unexplained m aturity o nset d iabetes of the y oung (MODY)-like diabetes and an apparently balanced translocation [46,XY,t(7;10)(q22;p12)] and sought to identify a novel diabetes locus by characterizing the translocation breakpoints.

Results

Mutations in coding exons and splice sites of known MODY genes were first ruled out by PCR amplification and DNA sequencing. Fluorescent in situ hybridization (FISH) studies demonstrated that the translocation did not disrupt two known diabetes-related genes on 10p12. The translocation breakpoints were further mapped to high resolution using FISH and somatic cell hybrids and the junctions PCR-amplified and sequenced. The translocation did not disrupt any annotated transcription unit. However, the chromosome 10 breakpoint was 220 kilobases 5' to the Membrane Protein, Palmitoylated 7 (MPP7) gene, which encodes a protein required for proper cell polarity. This biological function is shared by HNF4A, a known MODY gene. Databases show MPP7 is highly expressed in mouse pancreas and is expressed in human islets. The translocation did not appear to alter lymphoblastoid expression of MPP7 or other genes near the breakpoints.

Conclusion

The balanced translocation and MODY-like diabetes in the proband could be coincidental. Alternatively, the translocation may cause islet cell dysfunction by altering MPP7 expression in a subtle or tissue-specific fashion. The potential roles of MPP7 mutations in diabetes and perturbed islet cell polarity in insulin secretion warrant further study.
Achieving professional status: Australian podiatrists’ perceptions
Authors: Borthwick Alan M , Nancarrow Susan A , Vernon Wesley , Walker Jeremy
Published: February 2009

Background

This paper explores the notion of professional status from the perspective of a sample of Australian podiatrists; how it is experienced, what factors are felt to affect it, and how these are considered to influence professional standing within an evolving healthcare system. Underpinning sociological theory is deployed in order to inform and contextualise the study.

Methods

Data were drawn from a series of in‐depth semi‐structured interviews (n = 21) and focus groups (n = 9) with podiatrists from across four of Australia's eastern states (Queensland, New South Wales, Victoria and Australian Capital Territory), resulting in a total of 76 participants. Semi‐structured interview schedules sought to explore podiatrist perspectives on a range of features related to professional status within podiatry in Australia.

Results

Central to the retention and enhancement of status was felt to be the development of specialist roles and the maintenance of control over key task domains. Key distinctions in private and public sector environments, and in rural and urban settings, were noted and found to reflect differing contexts for status development. Marketing was considered important to image enhancement, as was the cache attached to the status of the universities providing graduate education.

Conclusion

Perceived determinants of professional status broadly matched those identified in the wider sociological literature, most notably credentialism, client status, content and context of work (such as specialisation) and an ideological basis for persuading audiences to acknowledge professional status. In an environment of demographic and workforce change, and the resultant policy demands for healthcare service re‐design, enhanced opportunities for specialisation appear evident. Under the current model of professionalism, both role flexibility and uniqueness may prove important.
The effect of diabetes mellitus on organ dysfunction with sepsis: an epidemiological study
Authors: Esper Annette M , Moss Marc , Martin Greg S
Published: February 2009

Introduction

Diabetes mellitus (DM) is one of the most common chronic co-morbid medical conditions in the USA and is frequently present in patients with sepsis. Previous studies reported that people with DM and severe sepsis are less likely to develop acute lung injury (ALI). We sought to determine whether organ dysfunction differed between people with and without DM and sepsis.

Methods

Using the National Hospital Discharge Survey US, sepsis cases from 1979 to 2003 were integrated with DM prevalence from the Centers for Disease Control and Prevention (CDC) Diabetes Surveillance System.

Results

During the study period 930 million acute-care hospitalisations and 14.3 million people with DM were identified. Sepsis occurred in 12.5 million hospitalisations and DM was present in 17% of patients with sepsis. In the population, acute respiratory failure was the most common organ dysfunction (13%) followed by acute renal failure (6%). People with DM were less likely to develop acute respiratory failure (9% vs. 14%, p < 0.05) and more likely to develop acute renal failure (13% vs. 7%, p < 0.05). Of people with DM and sepsis, 27% had a respiratory source of infection compared with 34% in people with no DM (p < 0.05). Among patients with a pulmonary source of sepsis, 16% of those with DM and 23% of those with no DM developed acute respiratory failure (p < 0.05); in non-pulmonary sepsis acute respiratory failure occurred in 6% of people with DM and 10% in those with no DM (p < 0.05).

Conclusions

In sepsis, people with diabetes are less likely to develop acute respiratory failure, irrespective of source of infection. Future studies should determine the relationship of these findings to reduced risk of ALI in people with DM and causative mechanisms.
Use of high-density tiling microarrays to identify mutations globally and elucidate mechanisms of drug resistance in Plasmodium falciparum
Authors: Dharia Neekesh V , Sidhu Amar Bir Singh , Cassera María Belén , Westenberger Scott J , Bopp Selina ER , Eastman Rich T , Plouffe David , Batalov Serge , Park Daniel J , Volkman Sarah K , Wirth Dyann F , Zhou Yingyao , Fidock David A , Winzeler Elizabeth A
Published: February 2009

Background

The identification of genetic changes that confer drug resistance or other phenotypic changes in pathogens can help optimize treatment strategies, support the development of new therapeutic agents, and provide information about the likely function of genes. Elucidating mechanisms of phenotypic drug resistance can also assist in identifying the mode of action of uncharacterized but potent antimalarial compounds identified in high-throughput chemical screening campaigns against Plasmodium falciparum.

Results

Here we show that tiling microarrays can detect de novo a large proportion of the genetic changes that differentiate one genome from another. We show that we detect most single nucleotide polymorphisms or small insertion deletion events and all known copy number variations that distinguish three laboratory isolates using readily accessible methods. We used the approach to discover mutations that occur during the selection process after transfection. We also elucidated a mechanism by which parasites acquire resistance to the antimalarial fosmidomycin, which targets the parasite isoprenoid synthesis pathway. Our microarray-based approach allowed us to attribute in vitro derived fosmidomycin resistance to a copy number variation event in the pfdxr gene, which enables the parasite to overcome fosmidomycin-mediated inhibition of isoprenoid biosynthesis.

Conclusions

We show that newly emerged single nucleotide polymorphisms can readily be detected and that malaria parasites can rapidly acquire gene amplifications in response to in vitro drug pressure. The ability to define comprehensively genetic variability in P. falciparum with a single overnight hybridization creates new opportunities to study parasite evolution and improve the treatment and control of malaria.
Impaired Insulin Exocytosis in Neural Cell Adhesion Molecule−/− Mice Due to Defective Reorganization of the Submembrane F-Actin Network
Authors: Olofsson Charlotta S. , Håkansson Joakim , Salehi Albert , Bengtsson Martin , Galvanovskis Juris , Partridge Chris , SörhedeWinzell Maria , Xian Xiaojie , Eliasson Lena , Lundquist Ingmar , Semb Henrik , Rorsman Patrik
Published: February 2009

The neural cell adhesion molecule (NCAM) is required for cell type segregation during pancreatic islet organogenesis. We have investigated the functional consequences of ablating NCAM on pancreatic β-cell function. In vivo, NCAM−/− mice exhibit impaired glucose tolerance and basal hyperinsulinemia. Insulin secretion from isolated NCAM−/− islets is enhanced at glucose concentrations below 15 mM but inhibited at higher concentrations. Glucagon secretion from pancreatic α-cells evoked by low glucose was also severely impaired in NCAM−/− islets. The diminution of insulin secretion is not attributable to defective glucose metabolism or glucose sensing (documented as glucose-induced changes in intracellular Ca2+ and KATP-channel activity). Resting KATP conductance was lower in NCAM−/− β-cells than wild-type cells, and this difference was abolished when F-actin was disrupted by cytochalasin D (1 μM). In wild-type β-cells, the submembrane actin network disassembles within 10 min during glucose stimulation (30 mM), an effect not seen in NCAM−/− β-cells. Cytochalasin D eliminated this difference and normalized insulin and glucagon secretion in NCAM−/− islets. Capacitance measurements of exocytosis indicate that replenishment of the readily releasable granule pool is suppressed in NCAM−/− α- and β-cells. Our data suggest that remodeling of the submembrane actin network is critical to normal glucose regulation of both insulin and glucagon secretion.