Systems analysis of iron metabolism: the network of iron pools and fluxes

Background  

Every cell of the mammalian organism needs iron as trace element in numerous oxido-reductive processes as well as for transport and storage of oxygen. The very versatility of ionic iron makes it a toxic entity which can catalyze the production of radicals that damage vital membranous and macromolecular assemblies in the cell. The mammalian organism maintains therefore a complex regulatory network of iron uptake, excretion and intra-body distribution. Intracellular regulation in different cell types is intertwined with a global hormonal signalling structure. Iron deficiency as well as excess of iron are frequent and serious human disorders. They can affect every cell, but also the organism as a whole.     

Starvation Resistance in a Stenothermal Species from the Indian Subcontinent: Mechanistic Basis of Clinal Variation

Parallel clines for starvation resistance and lipid content are well documented among drosophilids on the Indian subcontinent. However, the mechanistic basis of these clines has not been investigated so far. Here, we investigate the utilization of lipids during starvation as a function of duration of stress in D. ananassae. We found higher lipid content responsible for high starvation resistance at lower latitudes. Lipids were utilized during starvation only; not during any other climatic stresses like desiccation or thermal stresses. We also found a cline for consumption of total body lipids; as more content (out of total amount of lipids) was utilized by flies at lower latitudes and lesser at higher latitudes. But, there was no latitudinal cline for threshold lipid amount in the case of females while for males there was a positive cline. Lastly, parallel clines have evolved under contrasting climatic conditions i.e. drier and colder northern localities have flies with lower lipid and reduced starvation resistance while hot and humid localities favor flies with higher lipid levels and greater starvation tolerance. Thus, the evolution of clines associated with starvation and lipid content might have resulted due to specific ecological conditions i.e. humidity gradient on the Indian subcontinent.     

Mapping quantitative trait loci (QTL) in sheep. IV. Analysis of lactation persistency and extended lactation traits in sheep

Background

In sheep dairy production, total lactation performance, and length of lactation of lactation are of economic significance. A more persistent lactation has been associated with improved udder health. An extended lactation is defined by a longer period of milkability. This study is the first investigation to examine the presence of quantitative trait loci (QTL) for extended lactation and lactation persistency in sheep.

Methods

An (Awassi × Merino) × Merino single-sire backcross family with 172 ewes was used to map QTL for lactation persistency and extended lactation traits on a framework map of 189 loci across all autosomes. The Wood model was fitted to data from multiple lactations to estimate parameters of ovine lactation curves, and these estimates were used to derive measures of lactation persistency and extended lactation traits of milk, protein, fat, lactose, useful yield, and somatic cell score. These derived traits were subjected to QTL analyses using maximum likelihood estimation and regression analysis.

Results

Overall, one highly significant (LOD > 3.0), four significant (2.0 < LOD < 3.0) and five suggestive (1.7 < LOD < 2.0) QTL were detected across all traits in common by both mapping methods. One additional suggestive QTL was identified using maximum likelihood estimation, and four suggestive (0.01 < P < 0.05) and two significant (P < 0.01) QTL using the regression approach only. All detected QTL had effect sizes in the range of 0.48 to 0.64 SD, corresponding to QTL heritabilities of 3.1 to 8.9%. The comparison of the detected QTL with results in cattle showed conserved linkage regions. Most of the QTL identified for lactation persistency and extended lactation did not coincide. This suggests that persistency and extended lactation for the same as well as different milk yield and component traits are not controlled by the same genes.

Conclusion

This study identified ten novel QTL for lactation persistency and extended lactation in sheep, but results suggest that lactation persistency and extended lactation do not have a major gene in common. These results provide a basis for further validation in extended families and other breeds as well as targeting regions for genome-wide association mapping using high-density SNP arrays.     

Synthesis of a Nano-Silver Metal Ink for Use in Thick Conductive Film Fabrication Applied on a Semiconductor Package

The success of printing technology in the electronics industry primarily depends on the availability of metal printing ink. Various types of commercially available metal ink are widely used in different industries such as the solar cell, radio frequency identification (RFID) and light emitting diode (LED) industries, with limited usage in semiconductor packaging. The use of printed ink in semiconductor IC packaging is limited by several factors such as poor electrical performance and mechanical strength. Poor adhesion of the printed metal track to the epoxy molding compound is another critical factor that has caused a decline in interest in the application of printing technology to the semiconductor industry. In this study, two different groups of adhesion promoters, based on metal and polymer groups, were used to promote adhesion between the printed ink and the epoxy molding substrate. The experimental data show that silver ink with a metal oxide adhesion promoter adheres better than silver ink with a polymer adhesion promoter. This result can be explained by the hydroxyl bonding between the metal oxide promoter and the silane grouping agent on the epoxy substrate, which contributes a greater adhesion strength compared to the polymer adhesion promoter. Hypotheses of the physical and chemical functions of both adhesion promoters are described in detail.     

Reduced Infectivity of Adenovirus Type 5 Particles and Degradation of Entering Viral Genomes Associated with Incomplete Processing of the Preterminal Protein

To investigate further the contribution of the adenovirus type 5 (Ad5) E1B 55-kDa protein to genome replication, viral DNA accumulation was examined in primary human fibroblasts and epithelial cells infected with Ad5 or the E1B 55-kDa-null mutant Hr6. Unexpectedly, all cell types were observed to contain a significantly higher concentration of entering Hr6 than of Ad5 DNA, as did an infectious unit of Hr6. However, the great majority of the Hr6 genomes were degraded soon after entry. As this unusual phenotype cannot be ascribed to the Hr6 E1B frameshift mutation (J. S. Chahal and S. J. Flint, J. Virol. 86:3064–3072, 2012), the sequences of the Ad5 and Hr6 genomes were compared by using high-throughput sequencing. Seven previously unrecognized mutations were identified in the Hr6 genome, two of which result in substitutions in virion proteins, G315V in the preterminal protein (preTP) and A406V in fiber protein IV. Previous observations and the visualization by immunofluorescence of greater numbers of viral genomes entering the cytosol of Hr6-infected cells than of Ad5-infected cells indicated that the fiber mutation could not be responsible for the low-infectivity phenotype of Hr6. However, comparison of the forms of terminal protein present in purified virus particles indicated that the production of mature terminal protein from a processing intermediate is impaired in Hr6 particles. We therefore propose that complete processing of preTP within virus particles is necessary for the ability of viral genomes to become localized at appropriate sites and persist in infected cells.     

Sleep disturbance and cardiovascular risk in adolescents

Background:

Evidence suggests that inadequate or disturbed sleep is associated with increased cardiovascular risk in adults. There are limited data on sleep quality and associated cardiovascular risk in children.

Methods:

We obtained data on adolescents from the 2009/10 cycle of the Healthy Heart Schools’ Program, a population-based cross-sectional study in the Niagara region of Ontario. Participants underwent measurements of cardiometabolic risk factors, including body mass index (BMI), lipid profile and blood pressure, and they completed questionnaires measuring sleeping habits and nutritional status. We assessed sleep disturbance using the sleep disturbance score derived from the Pittsburgh Sleep Quality Index. We explored associations between sleeping habits and cardiovascular risk factors.

Results:

Among 4104 adolescents (51% male), the mean hours of sleep per night (± standard deviation) were 7.9 ± 1.1 on weeknights and 9.4 ± 1.6 on weekends. In total, 19% of participants reported their sleep quality as fairly bad or very bad on weeknights and 10% reported it as fairly bad or very bad on weekends. In the multivariable regression models, a higher sleep disturbance score was associated with increased odds of being at high cardiovascular risk (highest v. lowest tertile odds ratio [OR] 1.43 [95% confidence interval (CI) 1.16–1.77], p < 0.001), increased odds of hypertension (highest v. lowest tertile OR 1.44 [95% CI 1.02–2.05], p = 0.05) and increased odds of elevated non-high density lipoprotein cholesterol (highest v. lowest tertile OR 1.28 [95% CI 1.00–1.64], p = 0.05). The mean duration of sleep was not associated with these outcomes.

Interpretation:

In healthy adolescents, sleep disturbance is associated with cardiovascular risk factor abnormalities. Intervention strategies to optimize sleep hygiene early in life may be important for the prevention of cardiovascular disease.There is emerging evidence in experimental and epidemiologic studies that sleep parameters, specifically sleep duration and quality, are associated with cardiovascular outcomes, including hypertension,¹ as well as diabetes,² hypercholesterolemia³ and obesity.⁴ A recent meta-analysis involving 400 000 adults concluded that short sleep duration was associated with a greater risk of developing or dying from coronary heart disease.⁵ On average, adolescents sleep less than 8 hours per night,⁶ less than the recommended 9 hours,⁷ and about 20% of adolescents have significant sleep problems.⁶ Despite this knowledge, there is a paucity of epidemiologic research on the cardiovascular consequences of short sleep duration and impaired sleep quality in adolescents.In this study, we investigated the association between sleep disturbance and duration and measures of cardiovascular disease risk, including cholesterol, hypertension, body mass index (BMI) and dietary factors in adolescents.     

Supervised Lowess normalization of comparative genome hybridization data – application to lactococcal strain comparisons

Background

Visualising the evolutionary history of a set of sequences is a challenge for molecular phylogenetics. One approach is to use undirected graphs, such as median networks, to visualise phylogenies where reticulate relationships such as recombination or homoplasy are displayed as cycles. Median networks contain binary representations of sequences as nodes, with edges connecting those sequences differing at one character; hypothetical ancestral nodes are invoked to generate a connected network which contains all most parsimonious trees. Quasi-median networks are a generalisation of median networks which are not restricted to binary data, although phylogenetic information contained within the multistate positions can be lost during the preprocessing of data. Where the history of a set of samples contain frequent homoplasies or recombination events quasi-median networks will have a complex topology. Graph reduction or pruning methods have been used to reduce network complexity but some of these methods are inapplicable to datasets in which recombination has occurred and others are procedurally complex and/or result in disconnected networks.

Results

We address the problems inherent in construction and reduction of quasi-median networks. We describe a novel method of generating quasi-median networks that uses all characters, both binary and multistate, without imposing an arbitrary ordering of the multistate partitions. We also describe a pruning mechanism which maintains at least one shortest path between observed sequences, displaying the underlying relations between all pairs of sequences while maintaining a connected graph.

Conclusion

Application of this approach to 5S rDNA sequence data from sea beet produced a pruned network within which genetic isolation between populations by distance was evident, demonstrating the value of this approach for exploration of evolutionary relationships.