Genomic ancestry, self-reported "color" and quantitative measures of skin pigmentation in Brazilian admixed siblings

A current concern in genetic epidemiology studies in admixed populations is that population stratification can lead to spurious results. The Brazilian census classifies individuals according to self-reported "color", but several studies have demonstrated that stratifying according to "color" is not a useful strategy to control for population structure, due to the dissociation between self-reported "color" and genomic ancestry. We report the results of a study in a group of Brazilian siblings in which we measured skin pigmentation using a reflectometer, and estimated genomic ancestry using 21 Ancestry Informative Markers (AIMs). Self-reported "color", according to the Brazilian census, was also available for each participant. This made it possible to evaluate the relationship between self-reported "color" and skin pigmentation, self-reported "color" and genomic ancestry, and skin pigmentation and genomic ancestry. We observed that, although there were significant differences between the three "color" groups in genomic ancestry and skin pigmentation, there was considerable dispersion within each group and substantial overlap between groups. We also saw that there was no good agreement between the "color" categories reported by each member of the sibling pair: 30 out of 86 sibling pairs reported different "color", and in some cases, the sibling reporting the darker "color" category had lighter skin pigmentation. Socioeconomic status was significantly associated with self-reported "color" and genomic ancestry in this sample. This and other studies show that subjective classifications based on self-reported "color", such as the one that is used in the Brazilian census, are inadequate to describe the population structure present in recently admixed populations. Finally, we observed that one of the AIMs included in the panel (rs1426654), which is located in the known pigmentation gene SLC24A5, was strongly associated with skin pigmentation in this sample.     

Immune and inflammatory responses to Leishmania amazonensis isolated from different clinical forms of human leishmaniasis in CBA mice

Leishmania amazonensis causes different diseases depending on the host and parasitic virulence factors. In this study, CBA mice were infected with L. amazonensis isolates from patients with localized (Ba125), diffuse cutaneous (Ba276) or visceral leishmaniasis (Ba109). Mice infected with Ba125 and Ba276 progressed rapidly and lesions displayed an infiltrate rich in parasitized macrophages and were necrotic and ulcerated. Ba109 induced smaller lesions and a mixed inflammatory infiltrate without necrosis or ulceration. Ba109 induced an insidious disease with lower parasite load in CBA mice, similar to human disease. Levels of IFN-γ, IL-4 and IL-10 did not differ among the groups. Because all groups were unable to control the infection, expression of IL-4 associated with low production of IFN-γ in the early phase of infection may account for susceptibility, but others factors may contribute to the differences observed in inflammatory responses and infection progression. Evaluation of some parasitic virulence factors revealed that Ba276 exhibits higher ecto-ADPase and 5'-nucleotidase activities compared to the Ba109 and Ba125 strains. Both Ba276 and Ba125 had higher arginase activity in comparison to Ba109. Finally, these data suggest that the differences in enzyme activities among parasites can account for differences in host inflammatory responses and infection progression.     

Microbiome resilience of Amazonian forests: Agroforest divergence to bacteria and secondary forest succession convergence to fungi

An alarming and increasing deforestation rate threatens Amazon tropical ecosystems and subsequent degradation due to frequent fires. Agroforestry systems (AFS) may offer a sustainable alternative, reportedly mimicking the plant–soil interactions of the natural mature forest (MF). However, the role of microbial community in tropical AFS remains largely unknown. This knowledge is crucial for evaluating the sustainability of AFS and practices given the key role of microbes in the aboveground–belowground interactions. The current study, by comparing different AFS and successions of secondary and MFs, showed that AFS fostered distinct groups of bacterial community, diverging from the MFs, likely a result of management practices while secondary forests converged to the same soil microbiome found in the MF, by favoring the same groups of fungi. Model simulations reveal that AFS would require profound changes in aboveground biomass and in soil factors to reach the same microbiome found in MFs. In summary, AFS practices did not result in ecosystems mimicking natural forest plant–soil interactions but rather reshaped the ecosystem to a completely different relation between aboveground biomass, soil abiotic properties, and the soil microbiome.     

Alanyl-glutamine and glutamine plus alanine supplements improve skeletal redox status in trained rats: Involvement of heat shock protein pathways

Aims

We hypothesized that oral l-glutamine supplementations could attenuate muscle damage and oxidative stress, mediated by glutathione (GSH) in high-intensity aerobic exercise by increasing the 70-kDa heat shock proteins (HSP70) and heat shock factor 1 (HSF1).

Main methods

Adult male Wistar rats were 8-week trained (60-min/day, 5 days/week) on a treadmill. During the last 21 days, the animals were supplemented with either l-alanyl-l-glutamine dipeptide (1.5 g/kg, DIP) or a solution containing the amino acids l-glutamine (1 g/kg) and l-alanine (0.67 g/kg) in their free form (GLN + ALA) or water (controls).

Key findings

Plasma from both DIP- and GLN + ALA-treated animals showed higher l-glutamine concentrations and reduced ammonium, malondialdehyde, myoglobin and creatine kinase activity. In the soleus and gastrocnemius muscle of both supplemented groups, l-glutamine and GSH contents were increased and GSH disulfide (GSSG) to GSH ratio was attenuated (p < 0.001). In the soleus muscle, cytosolic and nuclear HSP70 and HSF1 were increased by DIP supplementation. GLN + ALA group exhibited higher HSP70 (only in the nucleus) and HSF1 (cytosol and nucleus). In the gastrocnemius muscle, both supplementations were able to increase cytosolic HSP70 and cytosolic and nuclear HSF1.

Significance

In trained rats, oral supplementation with DIP or GLN + ALA solution increased the expression of muscle HSP70, favored muscle l-glutamine/GSH status and improved redox defenses, which attenuate markers of muscle damage, thus improving the beneficial effects of high-intensity exercise training.     

Mycobacterial codon optimization of the gene encoding the Sm14 antigen of Schistosoma mansoni in recombinant Mycobacterium bovis Bacille Calmette-Guérin enhances protein expression but not protection against cercarial challenge in mice

A mycobacterial codon-optimized gene encoding the Sm14 antigen of Schistosoma mansoni was generated using oligonucleotide assembly. This synthetic gene enhanced approximately fourfold the protein expression level in recombinant Mycobacterium bovis Bacille Calmette-Guérin (rBCG) when compared to that obtained using the native gene in the same expression vector. Immunization of mice with rBCG expressing Sm14 via the synthetic gene induced specific cellular Th1-predominant immune responses, as determined by interferon-gamma production of Sm14-stimulated splenocytes, which were comparable to those recorded in animals immunized with an rBCG strain expressing the native gene. Administration of a single dose of the rBCG-Sm14 construct carrying the synthetic gene conferred protection against cercarial challenge in outbred Swiss mice, at a level equivalent to those provided by either a single dose of rBCG expressing the native gene or three doses of Escherichia coli-derived recombinant Sm14. Our data demonstrated that despite improving the level of antigen expression, the codon optimization strategy did not result in enhanced immunity or protection against cercarial S. mansoni challenge.     

Integrating life cycle assessment (LCA) and life cycle costing (LCC) in the early phases of aircraft structural design: an elevator case study

Purpose

The main objective of this paper is to develop a model that will combine economic and environmental assessment tools to support the composite material selection of aircraft structures in the early phases of design and application of the tool for an aircraft elevator.

Methods

An integrated life cycle cost (LCC) and life cycle assessment (LCA) methodology was used as part of the sustainable design approach for the laminate stacking sequence design. The model considered is the aircraft structure made of carbon fiber reinforce plastic prepreg and processed via hand layup-autoclave process which is the preferred method for the aircraft industry. The model was applied to a cargo aircraft elevator case study by comparing six different laminate configurations and two different carbon fiber prepreg materials across aircraft’s entire life cycle.

Results and discussion

The results show, in line with other studies using different methodologies (e.g., life cycle engineering, or LCE), that the combination of LCA with LCC is a worthwhile approach for comparing the different laminate configurations in terms of cost and environmental impact to support composite laminate stacking design by providing the best trade-off between cost and environment. Elevator LCC reduces 19% by changing the material type and applying different ply orientations. Elevator LCA score reduces 53% by selecting the optimum instead of best technical solution that minimizes the displacement. Improving the structural performance does not always lead to an increase in the cost.

     

Persistent activation of omentum influences the pattern of muscular lesion in the mdx diaphragm

The mdx (X chromosome-linked muscular dystrophy) mouse develops a multi-staged disorder characterized by muscle degeneration and reactive fibrosis. Skeletal muscles of mdx mice are not equally susceptible to degeneration. The aim of this study was to verify whether the intense remodeling of the mdx diaphragm could be attributed to influences from the peritoneal microenvironment and omentum, a lymphohematopoietic tissue rich in progenitor cells and trophic factors. At ages corresponding to increased muscular regeneration (12?weeks) and activation of fibrosis (24?weeks), the mdx omentum exhibited (1) morphological and functional characteristics of activation with enlarged milk-spots, an accumulation of CD4⁺, CD8⁺ and CD19⁺B220⁺ B lymphocytes; (2) the formation of clusters positive for proliferating cell nuclear antigen, mainly in B220⁺-rich areas organized in a follicular structure with a germinative center without any challenge by external antigen inducers; (3) clusters with cells positive for fibroblast growth factor-2, numerous Sca-1⁺CD3^-CD19^-Mac-1^- progenitor cells and increased CD4⁺, CD8⁺ and CD3⁺NK1.1⁺ cells in the peritoneal cavity. Omentectomy reduced areas with F4/80⁺ inflammatory infiltrate the activity of matrix metalloproteases 9 and 2, collagen deposition and areas with regenerating myofibers in the diaphragm. Thus, persistent activation of the omentum influences the pattern of inflammation and regeneration of the mdx diaphragm partly via the activation of progenitor cells and the production of growth factors that influence the physiopathology of the muscular tissue remodeling.     

Increasing glucose determination range by flow injection analysis (FIA) using glucose oxidase immobilised on polyaniline

A Flow Injection Analysis (FIA) for glucose using glucose oxidase (E.C.1.1.3.4) was developed. The enzyme was immobilised on polyaniline chemically synthetized on internal surface of silicon tube (2.0 mm of diameter and length from 1 to 5 meters), using glutaraldehyde as a bifunctional agent. The system was able to measure glucose at levels from 5 to 500mM with a response time of 2min using 250l of sample. The system has been operated satisfactorily for one month with more than 300 assays with loss of 60% of activity.