Broad clinical involvement in a family affected by the fragile X premutation

The mutations in the FMR1 gene have been described as a family of disorders called fragile X-associated disorders including fragile X syndrome, fragile X-associated tremor/ataxia syndrome, primary ovarian insufficiency, and other problems associated with the premutation, such as hypothyroidism, hypertension, neuropathy, anxiety, depression, attention-deficit hyperactivity disorders, and autism spectrum disorders. The premutation is relatively common in the general population affecting 1 of 130 to 250 female individuals and 1 of 250 to 800 male individuals. Therefore, to provide appropriate treatment and genetic counseling for all of the carriers and affected individuals in a family, a detailed family history that reviews many of the disorders that are related to both the premutation and the full mutation should be carried out as exemplified in these cases. To facilitate the integration of this knowledge into clinical practice, this is the first case report that demonstrates only premutation involvement across 3 generations

Ultra-fast responsive colloidal-polymer composite-based volatile organic compounds (VOC) sensor using nanoscale easy tear process

There is an immense need for developing a simple, rapid, and inexpensive detection assay for health-care applications or monitoring environments. To address this need, a photonic crystal (PC)-based sensor has been extensively studied due to its numerous advantages such as colorimetric measurement, high sensitivity, and low cost. However, the response time of a typical PC-based sensor is relatively slow due to the presence of the inevitable upper residual layer in colloidal structures. Hence, we propose an ultra-fast responsive PC-based volatile organic compound (VOC) sensor by using a "nanoscale easy tear (NET) process" inspired by commercially available "easy tear package". A colloidal crystal-polydimethylsiloxane (PDMS) composite can be successfully realized through nanoscale tear propagation along the interface between the outer surface of crystallized nanoparticles and bulk PDMS. The response time for VOC detection exhibits a significant decrease by allowing the direct contact with VOCs, because of perfect removal of the residual on the colloidal crystals. Moreover, vapor-phase VOCs can be monitored, which had been previously impossible. High-throughput production of the patterned colloidal crystal-polymer composite through the NET process can be applied to other multiplexed selective sensing applications or may be used for nanomolding templates

Synapse Pathology in Psychiatric and Neurologic Disease

Inhibitory and excitatory synapses play a fundamental role in information processing in the brain. Excitatory synapses usually are situated on dendritic spines, small membrane protrusions that harbor glutamate receptors and postsynaptic density components and help transmit electrical signals. In recent years, it has become evident that spine morphology is intimately linked to synapse function—smaller spines have smaller synapses and support reduced synaptic transmission. The relationship between synaptic signaling, spine shape, and brain function is never more apparent than when the brain becomes dysfunctional. Many psychiatric and neurologic disorders, ranging from mental retardation and autism to Alzheimer’s disease and addiction, are accompanied by alterations in spine morphology and synapse number. In this review, we highlight the structure and molecular organization of synapses and discuss functional effects of synapse pathology in brain disease

Diffusion in crowded biological environments: applications of Brownian dynamics

Biochemical reactions in living systems occur in complex, heterogeneous media with total concentrations of macromolecules in the range of 50 - 400 mgml. Molecular species occupy a significant fraction of the immersing medium, up to 40% of volume. Such complex and volume-occupied environments are generally termed 'crowded' and/or 'confined'. In crowded conditions non-specific interactions between macromolecules may hinder diffusion - a major process determining metabolism, transport, and signaling. Also, the crowded media can alter, both qualitatively and quantitatively, the reactions in vivo in comparison with their in vitro counterparts. This review focuses on recent developments in particle-based Brownian dynamics algorithms, their applications to model diffusive transport in crowded systems, and their abilities to reproduce and predict the behavior of macromolecules under in vivo conditions

Cytogenetic abnormalities and fragile-x syndrome in Autism Spectrum Disorder

BACKGROUND: Autism is a behavioral disorder with impaired social interaction, communication, and repetitive and stereotypic behaviors. About 5–10 % of individuals with autism have 'secondary' autism in which an environmental agent, chromosome abnormality, or single gene disorder can be identified. Ninety percent have idiopathic autism and a major gene has not yet been identified. We have assessed the incidence of chromosome abnormalities and Fragile X syndrome in a population of autistic patients referred to our laboratory. METHODS: Data was analyzed from 433 patients with autistic traits tested using chromosome analysis and/or fluorescence in situ hybridization (FISH) and/or molecular testing for fragile X syndrome by Southern and PCR methods. RESULTS: The median age was 4 years. Sex ratio was 4.5 males to 1 female [354:79]. A chromosome (cs) abnormality was found in 14/421 [3.33 %] cases. The aberrations were: 4/14 [28%] supernumerary markers; 4/14 [28%] deletions; 1/14 [7%] duplication; 3/14 [21%] inversions; 2/14 [14%] translocations. FISH was performed on 23 cases for reasons other than to characterize a previously identified cytogenetic abnormality. All 23 cases were negative. Fragile-X testing by Southern blots and PCR analysis found 7/316 [2.2 %] with an abnormal result. The mutations detected were: a full mutation (fM) and abnormal methylation in 3 [43 %], mosaic mutations with partial methylation of variable clinical significance in 3 [43%] and a permutation carrier [14%]. The frequency of chromosome and fragile-X abnormalities appears to be within the range in reported surveys (cs 4.8-1.7%, FRAX 2–4%). Limitations of our retrospective study include paucity of behavioral diagnostic information, and a specific clinical criterion for testing. CONCLUSIONS: Twenty-eight percent of chromosome abnormalities detected in our study were subtle; therefore a high resolution cytogenetic study with a scrutiny of 15q11.2q13, 2q37 and Xp23.3 region should be standard practice when the indication is autism. The higher incidence of mosaic fragile-X mutations with partial methylation compared to FRAXA positive population [50% vs 15–40%] suggests that faint bands and variations in the Southern band pattern may occur in autistic patients

Medical conditions in autism spectrum disorders

Autism spectrum disorder (ASD) is a behaviourally defined syndrome where the etiology and pathophysiology is only partially understood. In a small proportion of children with the condition, a specific medical disorder is identified, but the causal significance in many instances is unclear. Currently, the medical conditions that are best established as probable causes of ASD include Fragile X syndrome, Tuberous Sclerosis and abnormalities of chromosome 15 involving the 15q11-13 region. Various other single gene mutations, genetic syndromes, chromosomal abnormalities and rare de novo copy number variants have been reported as being possibly implicated in etiology, as have several ante and post natal exposures and complications. However, in most instances the evidence base for an association with ASD is very limited and largely derives from case reports or findings from small, highly selected and uncontrolled case series. Not only therefore, is there uncertainty over whether the condition is associated, but the potential basis for the association is very poorly understood. In some cases the medical condition may be a consequence of autism or simply represent an associated feature deriving from an underlying shared etiology. Nevertheless, it is clear that in a growing proportion of individuals potentially causal medical conditions are being identified and clarification of their role in etio-pathogenesis is necessary. Indeed, investigations into the causal mechanisms underlying the association between conditions such as tuberous sclerosis, Fragile X and chromosome 15 abnormalities are beginning to cast light on the molecular and neurobiological pathways involved in the pathophysiology of ASD. It is evident therefore, that much can be learnt from the study of probably causal medical disorders as they represent simpler and more tractable model systems in which to investigate causal mechanisms. Recent advances in genetics, molecular and systems biology and neuroscience now mean that there are unparalleled opportunities to test causal hypotheses and gain fundamental insights into the nature of autism and its development

Depth-related effects on a meiofaunal community dwelling in the periphyton of a mesotrophic lake

Kreuzinger B, Schroeder F, Majdi N, Traunspurger W. Depth-related effects on a meiofaunal community dwelling in the periphyton of a mesotrophic lake. PLoS One. 2015;10(9): e0137793.Periphyton is a complex assemblage of micro- and meiofauna embedded in the organic matrix that coats most submerged substrate in the littoral of lakes. The aim of this study was to better understand the consequences of depth-level fluctuation on a periphytic community. The effects of light and wave disturbance on the development of littoral periphyton were evaluated in Lake Erken (Sweden) using an experimental design that combined in situ shading with periphyton depth transfers. Free-living nematodes were a major contributor to the meiofaunal community. Their species composition was therefore used as a proxy to distinguish the contributions of light- and wave-related effects. The periphyton layer was much thicker at a depth of 30 cm than at 200 cm, as indicated by differences in the amounts of organic and phototrophic biomass and meiofaunal and nematode densities. A reduction of the depth-level of periphyton via a transfer from a deep to a shallow location induced rapid positive responses by its algal, meiofaunal, and nematode communities. The slower and weaker negative responses to the reverse transfer were attributed to the potentially higher resilience of periphytic communities to increases in the water level. In the shallow littoral of the lake, shading magnified the effects of phototrophic biomass erosion by waves, as the increased exposure to wave shear stress was not compensated for by an increase in photosynthesis. This finding suggests that benthic primary production will be strongly impeded in the shallow littoral zones of lakes artificially shaded by construction or embankments. However, regardless of the light constraints, an increased exposure to wave action had a generally positive short-term effect on meiofaunal density, by favoring the predominance of species able to anchor themselves to the substrate, especially the Chromadorid nematode Punctodora ratzeburgensis