bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

AbstractBackgroundThis 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.MethodsData 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.ResultsCentral 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.ConclusionPerceived 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

Abstract
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

Abstract
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.
The physiology of long-distance migration: extending the limits of endurance metabolism
Authors: Weber Jean-Michel 
Published: February 2009

SUMMARYLong-distance migrants have evolved specific adaptations that make their athletic records possible. Unique mechanisms explaining their amazing capacity for endurance exercise have now been uncovered, particularly with respect to energy storage, mobilization, transport and utilization. Birds are champions of migration because flying offers a key compromise: it allows more rapid movement than swimming, but has a lower cost of transport than running. High efficiency for muscle contraction, pointed wings, low wingloading, travelling in V-formations, storing fuel as energy-dense lipids and atrophy of non-essential organs are some of their strategies to decrease the cost of transport. The ability to process lipids rapidly also emerges as a crucial component of the migrant phenotype. High lipid fluxes are made possible by lipoprotein shuttles and fatty acid binding proteins (FABPs) that accelerate lipid transport and by upgrading the metabolic machinery for lipolysis and lipid oxidation. Preparation for long flights can include natural doping on n-3 polyunsaturated fatty acids (n-3 PUFAs) from unique invertebrate diets. Muscle performance is improved by restructuring membrane phospholipids and by activating key genes of lipid metabolism through peroxisome proliferator-activated receptors (PPARs). The physiological secret to long migrations does not depend on a single `magic' adaptation but on the integration of multiple adjustments in morphology, biomechanics, behavior,nutrition and metabolism. Research on the physiology of migrants improves the fundamental knowledge of exercise biology, but it also has important implications for wildlife conservation, treating obesity and improving the performance of human athletes.
Behavioral responses of big brown bats to dives by praying mantises
Authors: Ghose Kaushik , Triblehorn Jeffrey D. , Bohn Kari , Yager David D. , Moss Cynthia F. 
Published: February 2009

SUMMARYInsectivorous echolocating bats face a formidable array of defenses employed by their airborne prey. One such insect defense is the ultrasound-triggered dive, which is a sudden, rapid drop in altitude,sometimes all the way to the ground. Although many previous studies have investigated the dynamics of such dives and their effect on insect survival rate, there has been little work on how bats may adapt to such an insect defense employed in the middle of pursuit. In this study we investigated how big brown bats (Eptesicus fuscus) adjust their pursuit strategy when flying praying mantises (Parasphendale agrionina) execute evasive,ultrasound-triggered dives. Although the mantis dive occasionally forced the bat to completely abort its chase (25% trials), in a number of cases (75%trials) the bat followed the mantis into the dive. In such cases the bat kept its sonar beam locked onto the target and maneuvered to maintain the same time efficient strategy it adopted during level flight pursuit, though it was ultimately defeated by the dive. This study suggests that although the mantis dive can be effective in evading the bat, it does not always deter the bat from continuing pursuit and, given enough altitude, the bat can potentially capture diving prey using the same flight strategy it employs to intercept prey in level flight.
AMP-activated protein kinase (AMPK) in the rock crab,Cancer irroratus: an early indicator of temperature stress
Authors: Frederich Markus , O'Rourke Michaela R. , Furey Nathan B. , Jost Jennifer A. 
Published: February 2009

SUMMARYExposure of marine invertebrates to high temperatures leads to a switch from aerobic to anaerobic metabolism, a drop in the cellular ATP concentration([ATP]), and subsequent death. In mammals, AMP-activated protein kinase (AMPK)is a major regulator of cellular [ATP] and activates ATP-producing pathways,while inhibiting ATP-consuming pathways. We hypothesized that temperature stress in marine invertebrates activates AMPK to provide adequate concentrations of ATP at increased but sublethal temperatures and that AMPK consequently can serve as a stress indicator (similar to heat shock proteins,HSPs). We tested these hypotheses through two experiments with the rock crab, Cancer irroratus. First, crabs were exposed to a progressive temperature increase (6°C h–1) from 12 to 30°C. AMPK activity, total AMPK protein and HSP70 levels, reaction time, heart rate and lactate accumulation were measured in hearts at 2°C increments. AMPK activity remained constant between 12 and 18°C, but increased up to 9.1(±1.5)-fold between 18 and 30°C. The crabs' reaction time also decreased above 18°C. By contrast, HSP70 (total and inducible) and total AMPK protein expression levels did not vary significantly over this temperature range. Second, crabs were exposed for up to 6 h to the sublethal temperature of 26°C. This prolonged exposure led to a constant elevation of AMPK activity and levels of HSP70 mRNA. AMPK mRNA continuously increased,indicating an additional response in gene expression. We conclude that AMPK is an earlier indicator of temperature stress in rock crabs than HSP70,especially during the initial response to high temperatures. We discuss the temperature-dependent increase in AMPK activity in the context of Shelford's law of tolerance. Specifically, we describe AMPK activity as a cellular marker that indicates a thermal threshold, called the pejus temperature, Tp. At Tp the animals leave their optimum range and enter a temperature range with a limited aerobic scope for exercise. This Tp is reached periodically during annual temperature fluctuations and has higher biological significance than earlier described critical temperatures, at which the animals switch to anaerobic metabolism and HSP expression is induced.