Stimulating intellectual activity with adaptive environment (SMILE)

© 2017 Association for Computing Machinery. As of 2016, 47.5 million people have dementia worldwide according to the World Health Organization, and it is expected that this number will nearly double every 20 years, reaching 100 million sooner than 2030. The goal of the SMILE concept is to help the elderly to live independently and to prevent/delay dementia. It should improve the quality of life of elderly by introducing healthy habits and a lifelong involvement in mentally and socially stimulating activities. It should reduce social isolation, i.e. high degree of loneliness, dissatisfaction with social contacts, and decreased social network. The focus is on prevention of gradual decline in memory function and planning ability, as well. Applying social network concepts provides easier social interaction for older people. Using stimulating and interactive environment enhances and maintains brain plasticity through social interaction. So far there are no published articles or projects that are targeted at the same goal to develop a self-care social interactive TV system as a Service, which is the aim of the SMILE concept. There are a lot of projects and papers about the relevant technologies, however not the integrated approach, which is the key innovation in this concept

Computational biology tools in design of an agrochemical against Xyllela fastidiosa.

Xylella fastidiosa is a Gram-negative, non-flagellated bacterium that causes CVC in citrus and Pierce?s disease in grapevines. The CVC affects 40% of the 200 million orange trees in São Paulo state. It colonizes the xylem vessels of the plants, blocking the water and nutrient flows. PilT protein is a part of the motility system and very important for Xyllela pathogenicity and our protein target for drug design. Computational biology tools were used to design the compound able to inhibit the formation of the PilT hexamer, leading to loss of Xyllela pathogenicity. This approach could be employed in the development of new inhibitors against different targets belonging to the same protein family of PilT

Computational Biology tools in design of an agrochemical against Xylella fastidiosa.

Since its pathogenicity is related to bacterial motility, the protein PilT from the twitching motility system has been chosen as the host target. Using rational drug design, based on a detailed comprehension of the protein host structure, small molecules were designed in order to block the activity of the protein and provoke the loss of the bacterium pathogenicity.C.016

Mapping contacts between regulatory domains of skeletal muscle TnC and Tnl by analyses of a single-chain chimeras.

The troponin (Tn) complex is formed by TnC, TnI and TnT and is responsible for the calcium-dependent inhibition of muscle contraction. TnC and TnI interact in an antiparallel fashion in which the N domain of TnC binds in a calcium-dependent manner to the C domain of TnI, releasing the inhibitory effect of the latter on the actomyosin interaction. While the crystal structure of the core cardiac muscle troponin complex has been determined, very little high resolution information is available regarding the skeletal muscle TnITnC complex. With the aim of obtaining structural information regarding specific contacts between skeletal muscle TnC and TnI regulatory domains, we have constructed two recombinant chimeric proteins composed of the residues 191 of TnC linked to residues 98182 or 98147 of TnI. The polypeptides were capable of binding to the thin filament in a calcium-dependent manner and to regulate the ATPase reaction of actomyosin. Small angle X-ray scattering results showed that these chimeras fold into compact structures in which the inhibitory plus the C domain of TnI, with the exception of residues 148182, were in close contact with the N-terminal domain of TnC. CD and fluorescence analysis were consistent with the view that the last residues of TnI (148182) are not well folded in the complex. MS analysis of fragments produced by limited trypsinolysis showed that the whole TnC N domain was resistant to proteolysis, both in the presence and in the absence of calcium. On the other hand the TnI inhibitory and C-terminal domains were completely digested by trypsin in the absence of calcium while the addition of calcium results in the protection of only residues 114137

Vapd In Xylella Fastidiosa Is A Thermostable Protein With Ribonuclease Activity.

Xylella fastidiosa strain 9a5c is a gram-negative phytopathogen that is the causal agent of citrus variegated chlorosis (CVC), a disease that is responsible for economic losses in Brazilian agriculture. The most well-known mechanism of pathogenicity for this bacterial pathogen is xylem vessel occlusion, which results from bacterial movement and the formation of biofilms. The molecular mechanisms underlying the virulence caused by biofilm formation are unknown. Here, we provide evidence showing that virulence-associated protein D in X. fastidiosa (Xf-VapD) is a thermostable protein with ribonuclease activity. Moreover, protein expression analyses in two X. fastidiosa strains, including virulent (Xf9a5c) and nonpathogenic (XfJ1a12) strains, showed that Xf-VapD was expressed during all phases of development in both strains and that increased expression was observed in Xf9a5c during biofilm growth. This study is an important step toward characterizing and improving our understanding of the biological significance of Xf-VapD and its potential functions in the CVC pathosystem.10e014576

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC): Compound heterozygous mutation in the claudin 16 (CLDN16) gene

<p>Abstract</p> <p>Background</p> <p>Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC) is an autosomal recessive disorder of renal calcium and magnesium wasting frequently complicated by progressive chronic renal failure in childhood or adolescence.</p> <p>Methods</p> <p>A 7 year old boy was investigated following the findings of marked renal insufficiency and nephrocalcinosis in his 18-month old sister. He too was found to have extensive nephrocalcinosis with increased fractional excretion of magnesium: 12.4% (<4%) and hypercalciuria: 5.7 mmol (< 2.5/24 hours). He had renal impairment, partial distal renal tubular acidosis and defective urinary concentrating ability. Therapy with thiazide diuretics and magnesium supplements failed to halt the progression of the disorder. Both children subsequently underwent renal transplantation. Both children's parents are unaffected and there is one unaffected sibling.</p> <p>Results</p> <p>Mutation analysis revealed 2 heterozygous mutations in the claudin 16 gene <it>(CLDN16</it>) in both affected siblings; one missense mutation in exon 4: C646T which results in an amino acid change Arg216Cys in the second extracellular loop of <it>CLDN16 </it>and loss of function of the protein and a donor splice site mutation which changes intron 4 consensus splice site from 'GT' to 'TT' resulting in decreased splice efficiency and the formation of a truncated protein with loss of 64 amino acids in the second extracellular loop.</p> <p>Conclusion</p> <p>The mutations in <it>CLDN16 </it>in this kindred affect the second extra-cellular loop of claudin 16. The clinical course and molecular findings suggest complete loss of function of the protein in the 2 affected cases and highlight the case for molecular diagnosis in individuals with FHHNC.</p