Causal Models of Clinically Significant Behaviors in Angelman, Cornelia de Lange, Prader-Willi and Smith-Magenis Syndromes

The operant learning theory account of behaviors of clinical significance in people with intellectual disability (ID) has dominated the field for nearly 50 years. However, in the last two decades, there has been a substantial increase in published research that describes the behavioral phenotypes of genetic disorders and shows that behaviors such as self-injury and aggression are more common in some syndromes than might be expected given group characteristics. These cross-syndrome differences in prevalence warrant explanation, not least because this observation challenges an exclusively operant learning theory account. To explore this possible conflict between theoretical account and empirical observation, we describe the genetic cause and physical, social, cognitive and behavioral phenotypes of four disorders associated with ID (Angleman, Cornelia de Lange, Prader-Willi and Smith-Magenis syndromes) and focus on the behaviors of clinical significance in each syndrome. For each syndrome we then describe a model of the interactions between physical characteristics, cognitive and motivational endophenotypes and environmental factors (including operant reinforcement) to account for the resultant behavioral phenotype. In each syndrome it is possible to identify pathways from gene to physical phenotype to cognitive or motivational endophenotype to behavior to environment and back to behavior. We identify the implications of these models for responsive and early intervention and the challenges for research in this area. We identify a pressing need for meaningful dialog between different disciplines to construct better informed models that can incorporate all relevant and robust empirical evidence.

Soil-Geochemical Factors controlling the Distribution and Oral Bioaccessibility of Nickel, Vanadium and Chromium in Northern Ireland Soils

Geogenic nickel (Ni), vanadium (V) and chromium (Cr) are present at elevated levels in soils in Northern Ireland. Whilst Ni, V and Cr total soil concentrations share common geological origins, their respective levels of oral bioaccessibility are influenced by different soil-geochemical factors. Oral bioaccessibility extractions were carried out on 145 soil samples overlying 9 different bedrock types to measure the bioaccessible portions of Ni, V and Cr. Principal component analysis identified two components (PC1 and PC2) accounting for 69% of variance across 13 variables from the Northern Ireland Tellus Survey geochemical data. PC1 was associated with underlying basalt bedrock, higher bioaccessible Cr concentrations and lower Ni bioaccessibility. PC2 was associated with regional variance in soil chemistry and hosted factors accounting for higher Ni and V bioaccessibility. Eight per cent of total V was solubilised by gastric extraction on average across the study area. High median proportions of bioaccessible Ni were observed in soils overlying sedimentary rock types. Whilst Cr bioaccessible fractions were low (max = 5.4%), the highest measured bioaccessible Cr concentration reached 10.0 mg kg-1, explained by factors linked to PC1 including high total Cr concentrations in soils overlying basalt bedrock.

Controlling the materials properties and nanostructure of a single-component dendritic gel by adding a second component

This paper reports a dendritic system which is capable of forming both one-component and two-component gels interestingly the addition of the second component can either increase or decrease the degree of gelation, depending on dendritic generation.

Spatially-resolved mapping of history-dependent coupled electrochemical and electronical behaviors of electroresistive NiO

Bias-induced oxygen ion dynamics underpins a broad spectrum of electroresistive and memristive phenomena in oxide materials. Although widely studied by device-level and local voltage-current spectroscopies, the relationship between electroresistive phenomena, local electrochemical behaviors, and microstructures remains elusive. Here, the interplay between history-dependent electronic transport and electrochemical phenomena in a NiO single crystalline thin film with a number of well-defined defect types is explored on the nanometer scale using an atomic force microscopy-based technique. A variety of electrochemically-active regions were observed and spatially resolved relationship between the electronic and electrochemical phenomena was revealed. The regions with pronounced electroresistive activity were further correlated with defects identified by scanning transmission electron microscopy. Using fully coupled mechanical-electrochemical modeling, we illustrate that the spatial distribution of strain plays an important role in electrochemical and electroresistive phenomena. These studies illustrate an approach for simultaneous mapping of the electronic and ionic transport on a single defective structure level such as dislocations or interfaces, and pave the way for creating libraries of defect-specific electrochemical responses.

Controlling Surface Topology and Functionality of Electrospun Fibers on the Nanoscale using Amphiphilic Block Copolymers To Direct Mesenchymal Progenitor Cell Adhesion

Surface patterning in three dimensions is of great importance in biomaterials design for controlling cell behavior. A facile one-step functionalization of biodegradable PDLLA fibers using amphiphilic diblock copolymers is demonstrated here to systematically vary the fiber surface composition. The copolymers comprise a hydrophilic poly[oligo(ethylene glycol) methacrylate] (POEGMA), poly[(2-methacryloyloxy)ethyl phosphorylcholine] (PMPC), or poly[2-(dimethylamino)ethyl methacrylate)] (PDMAEMA) block and a hydrophobic poly(l-lactide) (PLA) block. The block copolymer-modified fibers have increased surface hydrophilicity compared to that of PDLLA fibers. Mixtures of PLAPMPC and PLAPOEGMA copolymers are utilized to exploit microphase separation of the incompatible hydrophilic PMPC and POEGMA blocks at the fiber surface. Conjugation of an RGD cell-adhesive peptide to one hydrophilic block (POEGMA) using thiol-ene chemistry produces fibers with domains of cell-adhesive (POEGMA) and cell-inert (PMPC) sites, mimicking the adhesive properties of the extracellular matrix (ECM). Human mesenchymal progenitor cells (hES-MPs) showed much better adhesion to the fibers with surface-adhesive heterogeneity compared to that to fibers with only adhesive or only inert surface chemistries.

Lead-bismuth eutectic corrosion behaviors of ferritic/martensitic steels in low oxygen concentration environment

In order to investigate the compatibility of candidate structural materials with liquid metals, two kinds of ferritic/martensitic steels were chosen to contact with lead–bismuth eutectic in sealed quartz–glass tubes. The corrosion exposures were for 500 and 3000 h. Results showed that the oxidation layer and carbide dissolution layer on the two steels grew with contact time under oxygen unsaturated condition. Short-term corrosion behavior of a newly developed steel showed better lead–bismuth eutectic corrosion resistance than T91 at 873 K.

IRS2 and PTEN are key molecules in controlling insulin sensitivity in podocytes

Insulin signaling to the glomerular podocyte is important for normal kidney function and is implicated in the pathogenesis of diabetic nephropathy (DN). This study determined the role of the insulin receptor substrate 2 (IRS2) in this system. Conditionally immortalized murine podocytes were generated from wild-type (WT) and insulin receptor substrate 2-deficient mice (Irs2−/−). Insulin signaling, glucose transport, cellular motility and cytoskeleton rearrangement were then analyzed. Within the glomerulus IRS2 is enriched in the podocyte and is preferentially phosphorylated by insulin in comparison to IRS1. Irs2−/− podocytes are significantly insulin resistant in respect to AKT signaling, insulin-stimulated GLUT4-mediated glucose uptake, filamentous actin (F-actin) cytoskeleton remodeling and cell motility. Mechanistically, we discovered that Irs2 deficiency causes insulin resistance through up-regulation of the phosphatase and tensin homolog (PTEN). Importantly, suppressing PTEN in Irs2−/− podocytes rescued insulin sensitivity. In conclusion, this study has identified for the first time IRS2 as a critical molecule for sensitizing the podocyte to insulin actions through its ability to modulate PTEN expression. This finding reveals two potential molecular targets in the podocyte for modulating insulin sensitivity and treating DN.

Effects of temperature and strain rate on the tensile behaviors of SIMP steel in static lead bismuth eutectic

In order to assess the susceptibility of candidate structural materials to liquid metal embrittlement, this work investigated the tensile behaviors of ferritic-martensitic steel in static lead bismuth eutectic (LBE). The tensile tests were carried out in static lead bismuth eutectic under different temperatures and strain rates. Pronounced liquid metal embrittlement phenomenon is observed between 200 °C and 450 °C. Total elongation is reduced greatly due to the liquid metal embrittlement in LBE environment. The range of ductility trough is larger under slow strain rate tensile (SSRT) test.