Potential applications of stress solutes from extremophiles in protein folding diseases and healthcare

Protein misfolding, aggregation and deposition in the brain, in the form of amyloid, are implicated in the etiology of several neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and prion diseases. Drugs available on the market reduce the symptoms, but they are not a cure. Therefore, it is urgent to identify promising targets and develop effective drugs. Preservation of protein native conformation and/or inhibition of protein aggregation seem pertinent targets for drug development. Several studies have shown that organic solutes, produced by extremophilic microorganisms in response to osmotic and/or heat stress, prevent denaturation and aggregation of model proteins. Among these stress solutes, mannosylglycerate, mannosylglyceramide, di-myo-inositol phosphate, diglycerol phosphate and ectoine are effective in preventing amyloid formation by Alzheimer’s Aβ peptide and/or α-synuclein in vitro. Moreover, mannosylglycerate is a potent inhibitor of Aβ and α-synuclein aggregation in living cells, and mannosylglyceramide and ectoine inhibit aggregation and reduce prion peptide-induced toxicity in human cells. This review focuses on the efficacy of stress solutes from hyper/thermophiles and ectoines to prevent amyloid formation in vitro and in vivo and their potential application in drug development against protein misfolding diseases. Current and envisaged applications of these extremolytes in neurodegenerative diseases and healthcare will also be addressed.     

Absence of Tau triggers age‐dependent sciatic nerve morphofunctional deficits and motor impairment

Dementia is the cardinal feature of Alzheimer's disease (AD), yet the clinical symptoms of this disorder also include a marked loss of motor function. Tau abnormal hyperphosphorylation and malfunction are well‐established key events in AD neuropathology but the impact of the loss of normal Tau function in neuronal degeneration and subsequent behavioral deficits is still debated. While Tau reduction has been increasingly suggested as therapeutic strategy against neurodegeneration, particularly in AD, there is controversial evidence about whether loss of Tau progressively impacts on motor function arguing about damage of CNS motor components. Using a variety of motor‐related tests, we herein provide evidence of an age‐dependent motor impairment in Tau?/? animals that is accompanied by ultrastructural and functional impairments of the efferent fibers that convey motor‐related information. Specifically, we show that the sciatic nerve of old (17–22‐months) Tau?/? mice displays increased degenerating myelinated fibers and diminished conduction properties, as compared to age‐matched wild‐type (Tau+/+) littermates and younger (4–6 months) Tau?/? and Tau+/+ mice. In addition, the sciatic nerves of Tau?/? mice exhibit a progressive hypomyelination (assessed by g‐ratio) specifically affecting large‐diameter, motor‐related axons in old animals. These findings suggest that loss of Tau protein may progressively impact on peripheral motor system.     

Cognitive predictors of balance in Parkinson’s disease

Postural instability is one of the most incapacitating symptoms of Parkinson’s disease (PD) and appears to be related to cognitive deficits. This study aims to determine the cognitive factors that can predict deficits in static and dynamic balance in individuals with PD. A sociodemographic questionnaire characterized 52 individuals with PD for this work. The Trail Making Test, Rule Shift Cards Test, and Digit Span Test assessed the executive functions. The static balance was assessed using a plantar pressure platform, and dynamic balance was based on the Timed Up and Go Test. The results were statistically analysed using SPSS Statistics software through linear regression analysis. The results show that a statistically significant model based on cognitive outcomes was able to explain the variance of motor variables. Also, the explanatory value of the model tended to increase with the addition of individual and clinical variables, although the resulting model was not statistically significant The model explained 25–29% of the variability of the Timed Up and Go Test, while for the anteroposterior displacement it was 23–34%, and for the mediolateral displacement it was 24–39%. From the findings, we conclude that the cognitive performance, especially the executive functions, is a predictor of balance deficit in individuals with PD.     

Can the modeling for simplification of a dental implant surface affect the accuracy of 3D finite element analysis?

The aim of this study was to assess stress/strain of different implant modeling simplifications by 3D-FEA. Three variation of external hexagon implant (Ø3.75?×?10 mm) supporting one molar crown were simulated: A (no threads); B (slightly threads simplification); C (original design). 200 N (axial) and 100 N (oblique) were applied. Cortical bone was evaluated by maximum principal stress and microstrain qualitatively and quantitatively (ANOVA and Tukey post hoc (p < 0.05)). Higher stress levels (p < 0.05) were observed in model A. Models B and C presented similar stress transmission. It was possible to conclude that slightly simplification should be used for studies evaluating stress transferring for bone tissue.     

Riparian zone as a main determinant of the structure of lizard assemblages in upland Amazonian forests

The use of lizards as model organisms in ecological studies is based on their success in occupying a great diversity of habitats, and some species are closely tied to the environment, which is disadvantaged by the legislation of several countries concerning land use. Our aim was to relate lizard species distribution patterns in rainforest environments to variation in environmental gradients, and provide ecologically based metrics for establishing buffer zones around streams. Lizards were sampled three times in 41 standardised transects near Manaus, Brazil, only in dry season, with Time Limited Visual Search associated with raking through leaf litter. We recorded 20 species from 10 families and used non‐metric multidimensional scaling to reduce the dimensionality of quantitative and qualitative compositions of species. Multiple linear regression models indicated that the environmental gradients distance to nearest stream, extent of canopy openness, vegetation density and slope did not significantly influence assemblage species distribution, with an indication of effect of litter depth. By means of piecewise linear regression, the use of riparian zone was estimated at ~190 m from quantitative species composition and ~211 m from qualitative species composition. Five species occurred only in the riparian zone. Our results suggest that conservation of the entire riparian lizard assemblage in Amazonian rainforest is likely to require protection of at least a 211 m buffer on either side of streams.     

Leishmania infantum: mixed T-helper-1/T-helper-2 immune response in experimentally infected BALB/c mice

The main goal of the present study was to characterise the course of infection and immunological responses developed by Leishmania infantum infected BALB/c mice. Parasite load was determined by Real-time TaqMan PCR while cytokine and Immunoglobulin G (IgG) production were assessed by ELISA. Leishmania DNA was detected in spleen and liver as soon as day 1 post-inoculation (pi) and the parasitism was sustained until the end of the experiment. The cytokine kinetics in spleen and liver was generally associated with the oscillations of parasite load. Overall, it was not observed a distinct Th1 or Th2 pattern of cytokine production during the time of experiment. The infected mice developed a mixed immune response, with concomitant production of IFN-gamma, IL-4 and IL-10, both in spleen and liver, and both IgG isotypes. However, our results suggest that, compared to liver, the spleen is more susceptible to L. infantum infection.     

A novel mutation in DAX1 gene causing different phenotypes in three siblings with adrenal hypoplasia congenita

Adrenal hypoplasia congenita (AHC) is a rare disease that can be caused by many abnormalities, including an X-linked form. Mutations in the DAX1 gene have been assigned as the genetic cause of AHC. We describe here three siblings with AHC, clinically presented at different ages, two in the neonatal period and one oligosymptomatic during infancy. Molecular analysis was able to detect a novel mutation in exon 1 of the DAX1 gene, consisting of a transition of C to T at position 359, determining a stop codon at position 359 (Q359X). The mutated gene encodes a truncated protein missing a large portion of the ligand-binding domain (C-terminal domain). The recognition of the disease in the index case suggested the diagnosis in the other siblings. Interestingly, the same mutation is presented with different phenotypes, suggesting that first-degree family members of patients with DAX1 mutations should be carefully evaluated routinely.     

Music of metagenomics—a review of its applications,analysis pipeline,and associated tools

Functional & Integrative Genomics - This humble effort highlights the intricate details of metagenomics in a simple, poetic, and rhythmic way. The paper enforces the significance of the...