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 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

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

Distal renal tubular acidosis: ERKNet/ESPN clinical practice points

Distal renal tubular acidosis (dRTA) is characterised by an impaired ability of the distal tubule to excrete acid, leading to metabolic acidosis. Associated complications include bone disease, growth failure, urolithiasis and hypokalaemia. Due to its rarity, there is a limited evidence to guide diagnosis and management, however, available data strongly suggest that metabolic control of the acidosis by alkali supplementation can halt or revert almost all complications. Despite this, cohort studies show that adequate metabolic control is present in only about half of patients, highlighting problems with treatment provision or adherence. With these clinical practice points the authors, part of the working groups tubulopathies in the European Rare Kidney Disease Reference network (ERKnet) and inherited kidney diseases of the European Society for Paediatric Nephrology (ESPN) aim to provide guidance for the management of patients with dRTA to facilitate adequate treatment and establish an initial best practice standard against which treatment of patients can be audited

Aberrant Cortical Activity in Multiple GCaMP6-Expressing Transgenic Mouse Lines

Transgenic mouse lines are invaluable tools for neuroscience but, as with any technique, care must be taken to ensure that the tool itself does not unduly affect the system under study. Here we report aberrant electrical activity, similar to interictal spikes, and accompanying fluorescence events in some genotypes of transgenic mice expressing GCaMP6 genetically encoded calcium sensors. These epileptiform events have been observed particularly, but not exclusively, in mice with Emx1-Cre and Ai93 transgenes, of either sex, across multiple laboratories. The events occur at >0.1 Hz, are very large in amplitude (>1.0 mV local field potentials, >10% df/f widefield imaging signals), and typically cover large regions of cortex. Many properties of neuronal responses and behavior seem normal despite these events, although rare subjects exhibit overt generalized seizures. The underlying mechanisms of this phenomenon remain unclear, but we speculate about possible causes on the basis of diverse observations. We encourage researchers to be aware of these activity patterns while interpreting neuronal recordings from affected mouse lines and when considering which lines to study

Transgenic Mice for Intersectional Targeting of Neural Sensors and Effectors with High Specificity and Performance

SummaryAn increasingly powerful approach for studying brain circuits relies on targeting genetically encoded sensors and effectors to specific cell types. However, current approaches for this are still limited in functionality and specificity. Here we utilize several intersectional strategies to generate multiple transgenic mouse lines expressing high levels of novel genetic tools with high specificity. We developed driver and double reporter mouse lines and viral vectors using the Cre/Flp and Cre/Dre double recombinase systems and established a new, retargetable genomic locus, TIGRE, which allowed the generation of a large set of Cre/tTA-dependent reporter lines expressing fluorescent proteins, genetically encoded calcium, voltage, or glutamate indicators, and optogenetic effectors, all at substantially higher levels than before. High functionality was shown in example mouse lines for GCaMP6, YCX2.60, VSFP Butterfly 1.2, and Jaws. These novel transgenic lines greatly expand the ability to monitor and manipulate neuronal activities with increased specificity.Video Abstrac

Mutations in DSTYK and dominant urinary tract malformations.

ABSTRACT Introduction Congenital abnormalities of the kidney of the urinary tract are the most common cause of pediatric kidney failure. These disorders are highly heterogeneous, and their etiology is poorly understood. Methods We performed genome-wide linkage analysis and whole-exome sequencing in a family with autosomal dominant congenital abnormalities of the kidney of the urinary tract (7 affected family members). We also performed sequence analysis in 311 unrelated patients, as well as histologic and functional studies. Results Linkage analysis identified five regions of the genome that were shared among all affected family members. Exome sequencing identified a single rare deleterious variant within these linkage intervals, a heterozygous splice-site mutation in dual serine/threonine and tyrosine protein kinase (DSTYK). This variant, which resulted in aberrant gene product splicing, was present in all affected family members. Additional independent DSTYK mutations, including nonsense and splice-site mutations, were detected among 7/311 unrelated patients. DSTYK is highly expressed in the maturing epithelia of all major organs, localizing to cell membranes. Knockdown in zebrafish resulted in multi-organ developmental defects, resembling loss of fibroblast growth factor (FGF) signaling. Consistent with this finding, DSTYK colocalizes with FGF receptors in the ureteric bud and metanephric mesenchyme. Finally, DSTYK knockdown in human embryonic kidney cells inhibited FGF-stimulated ERK-phosphorylation, the principal signal downstream of receptor tyrosine kinases. Conclusions We detected DSTYK mutations in 2.2% of patients with congenital abnormalities of the kidney and urinary tract whom we studied, suggesting that DSTYK is a major determinant of human urinary tract development, downstream of FGF signaling