Increased nicotinamide nucleotide transhydrogenase levels predispose to insulin hypersecretion in a mouse strain susceptible to diabetes

Aims/hypothesis Insulin hypersecretion may be an independent predictor of progression to type 2 diabetes. Identifying genes affecting insulin hypersecretion are important in understanding disease progression. We have previously shown that diabetes-susceptible DBA/2 mice congenitally display high insulin secretion. We studied this model to map and identify the gene(s) responsible for this trait.

Methods Intravenous glucose tolerance tests followed by a genome-wide scan were performed on 171 (C57BL/6 × DBA/2) × C57BL/6 backcross mice.

Results A quantitative trait locus, designated hyperinsulin production-1 (Hip1), was mapped with a logarithm of odds score of 7.7 to a region on chromosome 13. Production of congenic mice confirmed that Hip1 influenced the insulin hypersecretion trait. By studying appropriate recombinant inbred mouse strains, the Hip1 locus was further localised to a 2 Mb interval, which contained only nine genes. Expression analysis showed that the only gene differentially expressed in islets isolated from the parental strains was Nnt, which encodes the mitochondrial proton pump, nicotinamide nucleotide transhydrogenase (NNT). We also found in five mouse strains a positive correlation (r 2  = 0.90, p < 0.01) between NNT activity and first-phase insulin secretion, emphasising the importance of this enzyme in beta cell function. Furthermore, of these five strains, only those with high NNT activity are known to exhibit severe diabetes after becoming obese.

Conclusions/interpretation Insulin hypersecretion is associated with increased Nnt expression. We suggest that NNT must play an important role in beta cell function and that its effect on the high insulin secretory capacity of the DBA/2 mouse may predispose beta cells of these mice to failure.

Dynamic strain-induced ferrite transformation during hot compression of low carbon Si-Mn steels

The dynamic strain-induced transformation (DSIT) of austenite to ferrite was investigated under different undercooling conditions using three low carbon Si-Mn steels. The undercooling of austenite (ΔT) was controlled by varying the cooling rate between austenitization and deformation temperatures. Uniform DSIT ferrite grains (∼2.3 μm) were produced at a relatively high deformation temperature above 840°C using a low carbon high Si steel (0.077C-0.97Mn-1.35Si, mass%) in connection with a larger ΔT. The critical conditions for DSIT were determined based on the flow stress-strain curves measured during hot compression tests. Influence of deformation temperature on DSIT of low carbon Si-added steel was also discussed.

Predators select against high growth rates and risk-taking behaviour in domestic trout populations

Domesticated (farm) salmonid fishes display an increased willingness to accept risk while foraging, and achieve high growth rates not observed in nature. Theory predicts that elevated growth rates in domestic salmonids will result in greater risk–taking to access abundant food, but low survival in the presence of predators. In replicated whole–lake experiments, we observed that domestic trout (selected for high growth rates) took greater risks while foraging and grew faster than a wild strain. However, survival consequences for greater growth rates depended upon the predation environment. Domestic trout experienced greater survival when risk was low, but lower survival when risk was high. This suggests that animals with high intrinsic growth rates are selected against in populations with abundant predators, explaining the absence of such phenotypes in nature. This is, to our knowledge, the first large–scale field experiment to directly test this theory and simultaneously quantify the initial invasibility of domestic salmonid strains that escape into the wild from aquaculture operations, and the ecological conditions affecting their survival.

Influence of grain size and training temperature on strain of polycrystalline Ni50Mn29Ga21 samples

The alloy Ni-Mn-Ga aroused great interest for application as a magnetic shape memory (MSM) material. This effect is caused by reorientation of twin variants by an external magnetic field. So far, most of the experiments were concentrated on single crystals. But, the MSM effect can also be realised in polycrystals which can be prepared much more efficiently. Here, polycrystalline samples were prepared by directional solidification with a <100> fibre texture of the high temperature cubic austenitic phase parallel to the heat flow. Afterwards, a heat treatment was applied for chemical homogenisation and stress relaxation in the austenitic state. Then the samples were heated up to the austenitic state and cooled down under load. The microstructure was analysed by Electron Back Scatter Diffraction (EBSD) before and after that treatment. Mechanical training at room temperature and 40°C was tracked by recording stress-strain curves. By increasing the number of training cycles the strain also increases. The influence of different training temperatures was investigated on samples with different grain sizes.

Fabrication, microstructure and mechanical properties of high performance ferrite-bainite steels

Low cost ferrite and bainite(FB) steels offer the prospect of high ultimate tensile strength combined with high hole expansion ratio. The enhanced strain hardening and formabilityof FB steels were primarily associated with the fine ferrite matrix, the low residual stresses and dislocation densityand compatible deformation between both phases.This overview describes the various techniques to produce FB steels, and comparestheresulting microstructure, tensile propertiesand tretchflangeabilitywith conventional HSLA and DP steels.A new generation of ultrafine ferrite and nano-scalebainiteautomotive steelsisunder development forthe futuredemands of extremely high strength and ductilitythroughthe fabricationtechnologiesinvolvingphase transformationsandplastic deformation.

An in situ method for the study of strain broadening using synchrotron X-ray diffraction

A tensonometer for stretching metal foils has been constructed for the study of strain broadening in X-ray diffraction line profiles. This device, which is designed for use on powder diffractometers and was tested on Station 2.3 at Daresbury Laboratory, allows in situ measurements to be performed on samples under stress. It can be used for data collection in either transmission or reflection modes using either symmetric or asymmetric diffraction geometries. As a test case, measurements were carried out on an 18 µm-thick copper foil experiencing strain levels of up to 5% using both symmetric reflection and symmetric transmission diffraction. All the diffraction profiles displayed peak broadening and asymmetry which increased with strain. The measured profiles were analysed by the fundamental-parameters approach using the TOPAS peak-fitting software. All the observed broadened profiles were modelled by convoluting a refineable diffraction profile, representing the dislocation and crystallite size broadening, with a fixed instrumental profile predetermined using high-quality LaB6 reference powder. The deconvolution process yielded `pure' sample integral breadths and asymmetry results which displayed a strong dependence on applied strain and increased almost linearly with applied strain. Assuming crystallite size broadening in combination with dislocation broadening arising from f.c.c. a/2〈110〉{111} dislocations, the variation of mechanical property with strain has been extracted. The observation of both peak asymmetry and broadening has been interpreted as a manifestation of a cellular structure with cell walls and cell interiors possessing high and low dislocation densities.

Effect of tensile pre-strain on bending and unloading of automotive steels

In recent years, advanced high strength steels (AHSS) have been used in a wide range of automotive applications; they may have property variations through the thickness and the properties may also be dependent of prior processing including pre-straining. In order to model forming processes precisely using, for example, finite element analysis, it is important that material input data should adequately reflect these effects. It is known that shape defects in roll forming are related to small strains in material that has undergone prior deformation in a different strain path. Much research has already been performed on the change in the Young’s Modulus once a steel sheet has been plastically deformed,however many of these tests have only been conducted using tensile testing, and therefore may not take into account differences in compressive and tensile unloading. This research investigates the effect of tensile pre-straining on bending behaviour for various types of material;in bending, one half of the sheet will load and unload in compression and hence experience deformation under a reversed stress. Four different materials were pre-strained in tension with 1%, 3%, 7%, 11% and 25% elongation. Using a free bending test, moment curvature diagrams were obtained for bending and unloading. The results showed that the characteristics of the moment curvature diagram depended on the degree of pre-straining; more highly strained samples showed an earlier elastic-plastic transformation and a decreased Young's Modulus during unloading. This was compared to previous literature results using only tensile tests. Our results could influence the modeling of springback in low tension sheet operations, such as roll forming.

On the low temperature strain aging of bainite in the TRIP steel

The aging behavior of a thermomechanically processed Mo-Al-Nb transformation-induced plasticity steel with ultrafine microstructure was investigated using transmission electron microscopy and atom probe tomography (APT). Strain aging at 73 K (200 °C) for 1800 seconds led to a significant bake-hardening response (up to 222 MPa). Moreover, aging for 1800 seconds at room temperature after 4 pct pre-strain also revealed a bake-hardening response (~60 MPa). The experimental results showed the formation of carbon Cottrell atmospheres around dislocations and the formation of carbon clusters/fine carbides in the bainitic ferrite during aging. It is proposed that this is associated with the high dislocation density of bainitic ferrite with formation of a complex dislocation substructure after pre-straining and its high average carbon content (~0.35 at. pct). The segregation of carbon and substitutional elements such as Mn and Mo to the retained austenite/bainitic ferrite interface during aging was observed by APT. This segregation is likely to be the preliminary stage for Mo-C particles’ formation. The aging after pre-straining also induced the decomposition of retained austenite with formation of ferrite and carbides.

Genome sequence of the clover-nodulating Rhizobium leguminosarum bv. trifolii strain SRDI565

Rhizobium leguminosarum bv. trifolii SRDI565 (syn. N8-J) is an aerobic,motile, Gram-negative, non-spore-forming rod. SRDI565 was isolated from anodule recovered from the roots of the annual clover Trifolium subterraneum subsp. subterraneum grown in thegreenhouse and inoculated with soil collected from New South Wales, Australia. SRDI565has a broad host range for nodulation within the clover genus, however N2-fixationis sub-optimal with some Trifoliumspecies and ineffective with others. Here we describe the features of R. leguminosarum bv. trifolii strain SRDI565, together with genomesequence information and annotation. The 6,905,599 bp high-quality-draft genomeis arranged into 7 scaffolds of 7 contigs, contains 6,750 protein-coding genesand 86 RNA-only encoding genes, and is one of 100 rhizobial genomes sequencedas part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia forBacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project.

Genome sequence of the clover-nodulating Rhizobium leguminosarum bv. trifolii strain SRDI943

Rhizobium leguminosarum bv. trifolii SRDI943(syn. V2-2) is an aerobic, motile, Gram-negative, non-spore-forming rod. SRDI943was isolated from a nodule recovered from the roots of the annual clover Trifoliummichelianum savi cv. paradanathat had been inoculated with a soil collected from a mixed pasture in Victoria, Australia. SRDI943 has a broadhost range for nodulation within the clover genus, however N2-fixationis sub-optimal (20-54% of reference strain WSM1325) on T. subterraneum spp.Here we describe the features of R. leguminosarum bv. trifolii strain SRDI943, together with genomesequence information and annotation. The 7,412,387 bp high-quality-draft genomeis arranged into 5 scaffolds of 5 contigs, contains 7,317 protein-coding genesand 89 RNA-only encoding genes, and is one of 100 rhizobial genomes sequencedas part of the DOE Joint Genome Institute 2010 Genomic Encylopedia for Bacteriaand Archaea-Root Nodule Bacteria (GEBA-RNB) project.

Job strain — attributable depression in a sample of working Australians: assessing the contribution to health inequalities

Background The broad aim of this study was to assess the contribution of job strain to mental health inequalities by (a) estimating the proportion of depression attributable to job strain (low control and high demand jobs), (b) assessing variation in attributable risk by occupational skill level, and (c) comparing numbers of job strain–attributable depression cases to numbers of compensated 'mental stress' claims. Methods Standard population attributable risk (PAR) methods were used to estimate the proportion of depression attributable to job strain. An adjusted Odds Ratio (OR) of 1.82 for job strain in relation to depression was obtained from a recently published meta-analysis and combined with exposure prevalence data from the Australian state of Victoria. Job strain exposure prevalence was determined from a 2003 population-based telephone survey of working Victorians (n = 1101, 66% response rate) using validated measures of job control (9 items, Cronbach's alpha = 0.80) and psychological demands (3 items, Cronbach's alpha = 0.66). Estimates of absolute numbers of prevalent cases of depression and successful stress-related workers' compensation claims were obtained from publicly available Australian government sources. Results Overall job strain-population attributable risk (PAR) for depression was 13.2% for males [95% CI 1.1, 28.1] and 17.2% [95% CI 1.5, 34.9] for females. There was a clear gradient of increasing PAR with decreasing occupational skill level. Estimation of job strain–attributable cases (21,437) versus "mental stress" compensation claims (696) suggest that claims statistics underestimate job strain–attributable depression by roughly 30-fold. Conclusion Job strain and associated depression risks represent a substantial, preventable, and inequitably distributed public health problem. The social patterning of job strain-attributable depression parallels the social patterning of mental illness, suggesting that job strain is an important contributor to mental health inequalities. The numbers of compensated 'mental stress' claims compared to job strain-attributable depression cases suggest that there is substantial under-recognition and under-compensation of job strain-attributable depression. Primary, secondary, and tertiary intervention efforts should be substantially expanded, with intervention priorities based on hazard and associated health outcome data as an essential complement to claims statistics.

Maternal supplementation with LGG reduces vaccine-specific immune responses in infants at high-risk of developing allergic disease

Probiotics are defined as live micro-organisms that when administered in adequate amounts confer a health benefit on the host. Among their pleiotropic effects, inhibition of pathogen colonization at the mucosal surface as well as modulation of immune responses are widely recognized as the principal biological activities of probiotic bacteria. In recent times, the immune effects of probiotics have led to their application as vaccine adjuvants, offering a novel strategy for enhancing the efficacy of current vaccines. Such an approach is particularly relevant in regions where infectious disease burden is greatest and where access to complete vaccination programs is limited. In this study, we report the effects of the probiotic, Lactobacillus rhamnosus GG (LGG) on immune responses to tetanus, Haemophilus influenzae type b (Hib) and pneumococcal conjugate (PCV7) vaccines in infants. This study was conducted as part of a larger clinical trial assessing the impact of maternal LGG supplementation in preventing the development of atopic eczema in infants at high-risk for developing allergic disease. Maternal LGG supplementation was associated with reduced antibody responses against tetanus, Hib, and pneumococcal serotypes contained in PCV7 (N = 31) compared to placebo treatment (N = 30) but not total IgG levels. Maternal LGG supplementation was also associated with a trend to increased number of tetanus toxoid-specific T regulatory in the peripheral blood compared to placebo-treated infants. These findings suggest that maternal LGG supplementation may not be beneficial in terms of improving vaccine-specific immunity in infants. Further clinical studies are needed to confirm these findings. As probiotic immune effects can be species/strain specific, our findings do not exclude the potential use of other probiotic bacteria to modulate infant immune responses to vaccines.

Genome sequence of Ensifer medicae strain WSM1115, an acid-tolerant Medicago-nodulating microsymbiont from Samothraki, Greece

Ensifer medicae (syn. Sinorhizobium medicae) strain WSM1115 forms effective nitrogen fixing symbioses with a range of annual Medicago species and is used in commercial inoculants in Australia. WSM1115 is an aerobic, motile, Gram-negative, non-spore-forming rod. It was isolated from a nodule recovered from the root of burr medic (Medicago polymorpha) collected on the Greek Island of Samothraki. WSM1115 has a broad host range for nodulation and N2 fixation capacity within the genus Medicago, although this does not extend to all medic species. WSM1115 is considered saprophytically competent in moderately acid soils (pHCaCl2 5.0) however, has failed to persist at field sites where soil salinity exceeded 10 ECe (dS/m). Here we describe the features of E. medicae strain WSM1115, together with genome sequence information and its annotation. The 6,861,065 bp high-quality-draft genome is arranged into 7 scaffolds of 28 contigs, contains 6,789 protein-coding genes and 83 RNA-only encoding genes, and is one of 100 rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project.

Genome sequence of Ensifer arboris strain LMG 14919T, a microsymbiont of the legume Prosopis chilensis growing in Kosti, Sudan

Ensifer arboris LMG 14919T is an aerobic, motile, Gram-negative, non-spore-forming rod that can exist as a soil saprophyte or as a legume microsymbiont of several species of legume trees. LMG 14919T was isolated in 1987 from a nodule recovered from the roots of the tree Prosopis chilensis growing in Kosti, Sudan. LMG 14919T is highly effective at fixing nitrogen with P. chilensis (Chilean mesquite) and Acacia senegal (gum Arabic tree or gum acacia). LMG 14919T does not nodulate the tree Leucena leucocephala, nor the herbaceous species Macroptilium atropurpureum, Trifolium pratense, Medicago sativa, Lotus corniculatus and Galega orientalis. Here we describe the features of E. arboris LMG 14919T, together with genome sequence information and its annotation. The 6,850,303 bp high-quality-draft genome is arranged into 7 scaffolds of 12 contigs containing 6,461 protein-coding genes and 84 RNA-only encoding genes, and is one of 100 rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project.

Genome sequence of Ensifer meliloti strain WSM1022, a highly effective microsymbiont of the model legume Medicago truncatula A17

Ensifer meliloti WSM1022 is an aerobic, motile, Gram-negative, non-spore-forming rod that can exist as a soil saprophyte or as a legume microsymbiont of Medicago. WSM1022 was isolated in 1987 from a nodule recovered from the roots of the annual Medicago orbicularis growing on the Cyclades Island of Naxos in Greece. WSM1022 is highly effective at fixing nitrogen with M. truncatula and other annual species such as M. tornata and M. littoralis and is also highly effective with the perennial M. sativa (alfalfa or lucerne). In common with other characterized E. meliloti strains, WSM1022 will nodulate but fixes poorly with M. polymorpha and M. sphaerocarpos and does not nodulate M. murex. Here we describe the features of E. meliloti WSM1022, together with genome sequence information and its annotation. The 6,649,661 bp high-quality-draft genome is arranged into 121 scaffolds of 125 contigs containing 6,323 protein-coding genes and 75 RNA-only encoding genes, and is one of 100 rhizobial genomes sequenced as part of the DOE Joint Genome Institute 2010 Genomic Encyclopedia for Bacteria and Archaea-Root Nodule Bacteria (GEBA-RNB) project.