The Autism Toolbox : An Autism Resource for Scottish Schools

The Autism Toolbox will draw upon a range of practice experience, literature and research to offer guidance for authorities and schools providing for children and young people with Autism Spectrum Disorders (ASD)

Calnexin Is Necessary for T Cell Transmigration into the Central Nervous System

In multiple sclerosis (MS), a demyelinating inflammatory disease of the CNS, and its animal model (experimental autoimmune encephalomyelitis; EAE), circulating immune cells gain access to the CNS across the blood-brain barrier to cause inflammation, myelin destruction, and neuronal damage. Here, we discovered that calnexin, an ER chaperone, is highly abundant in human brain endothelial cells of MS patients. Conversely, mice lacking calnexin exhibited resistance to EAE induction, no evidence of immune cell infiltration into the CNS, and no induction of inflammation markers within the CNS. Furthermore, calnexin deficiency in mice did not alter the development or function of the immune system. Instead, the loss of calnexin led to a defect in brain endothelial cell function that resulted in reduced T cell trafficking across the blood-brain barrier. These findings identify calnexin in brain endothelial cells as a potentially novel target for developing strategies aimed at managing or preventing the pathogenic cascade that drives neuroinflammation and destruction of the myelin sheath in MS

Microheterogeneity of Type II cAMP-Dependent Protein Kinase in Various Mammalian Species and Tissues

Excluding autophosphorylated species, at least six forms of the regulatory subunit of type II cAMP-dependent protein kinase (R(II)) from various mammalian tissues were identified by sodium dodecyl sulfate (SDS) gel electrophoresis of purified samples and of crude preparations photoaffinity labeled with 8-azido[32P] cAMP and by gel filtration. After autophosphorylation some heart R(II) forms termed type IIA (bovine, porcine, equine, and dog) shifted to a more slowly migrating band on SDS gels while others termed type IIB (rat, guinea pig, rabbit, and monkey) did not detectably shift. Both subclasses of R(II) exhibited variation in apparent M(r) on SDS gels. Bovine and porcine heart nonautophosphorylated R(II) had M(r) 56,000 and the autophosphorylated R(II) had M(r) 58,000, while dog and equine heart R(II) had M(r) 54,000 and 56,000 for these bands, respectively. Rat heart R(II) had M(r) 56,000 while rabbit and guinea pig heart R(II) had M(r) 52,000. More than one R(II) was found in different tissues of the same species. Rabbit skeletal muscle contained a M(r) 56,000 IIB form. Bovine lung contained almost equal amounts of a IIA form apparently identical to that of bovine heart and a M(r) 52,000 IIB form similar to that which predominated in bovine brain. Rat adipose tissue, brain, and monkey heart contained predominantly a M(r) 51,000 IIB form. The rat liver M(r) 56,000 IIB form chromatographed differently from all other R(II) tested by gel filtration. Several lines of evidence indicated that the various forms of R(II) were not derived from one another through proteolysis or other processes. Each of the type II forms rapidly incorporated 0.3-1.0 mol of 32P per mol of subunit when incubated with [γ-32P]ATP and C subunit. Four of the forms tested were similar in the cAMP concentration dependence for activation of their corresponding holoenzymes and inhibited C subunit about equally. Each exhibited two components of [3H]cAMP dissociation, indicating two intrachain cAMP-binding sites, and the dissociation rates for the respective sites, and the dissociation rates for the respective sites were similar

Trends in atmospheric evaporative demand in Great Britain using high-resolution meteorological data

Observations of climate are often available on very different spatial scales from observations of the natural environments and resources that are affected by climate change. In order to help bridge the gap between these scales using modelling, a new dataset of daily meteorological variables was created at 1 km resolution over Great Britain for the years 1961–2012, by interpolating coarser resolution climate data and including the effects of local topography. These variables were used to calculate atmospheric evaporative demand (AED) at the same spatial and temporal resolution. Two functions that represent AED were chosen: one is a standard form of potential evapotranspiration (PET) and the other is a derived PET measure used by hydrologists that includes the effect of water intercepted by the canopy (PETI). Temporal trends in these functions were calculated, with PET found to be increasing in all regions, and at an overall rate of 0.021 ± 0.021 mm day−1 decade−1 in Great Britain. PETI was found to be increasing at a rate of 0.019 ± 0.020 mm day−1 decade−1 in Great Britain, but this was not statistically significant. However, there was a trend in PETI in England of 0.023 ± 0.023 mm day−1 decade−1. The trends were found to vary by season, with spring PET increasing by 0.043 ± 0.019 mm day−1 decade−1 (0.038 ± 0.018 mm day−1 decade−1 when the interception correction is included) in Great Britain, while there is no statistically significant trend in other seasons. The trends were attributed analytically to trends in the climate variables; the overall positive trend was predominantly driven by rising air temperature, although rising specific humidity had a negative effect on the trend. Recasting the analysis in terms of relative humidity revealed that the overall effect is that falling relative humidity causes the PET to rise. Increasing downward short- and longwave radiation made an overall positive contribution to the PET trend, while decreasing wind speed made a negative contribution to the trend in PET. The trend in spring PET was particularly strong due to a strong decrease in relative humidity and increase in downward shortwave radiation in the spring

ER exit in physiology and disease

The biosynthetic secretory pathway is comprised of multiple steps, modifications and interactions that form a highly precise pathway of protein trafficking and secretion, that is essential for eukaryotic life. The general outline of this pathway is understood, however the specific mechanisms are still unclear. In the last 15 years there have been vast advancements in technology that enable us to advance our understanding of this complex and subtle pathway. Therefore, based on the strong foundation of work performed over the last 40 years, we can now build another level of understanding, using the new technologies available. The biosynthetic secretory pathway is a high precision process, that involves a number of tightly regulated steps: Protein folding and quality control, cargo selection for Endoplasmic Reticulum (ER) exit, Golgi trafficking, sorting and secretion. When deregulated it causes severe diseases that here we categorise into three main groups of aberrant secretion: decreased, excess and altered secretion. Each of these categories disrupts organ homeostasis differently, effecting extracellular matrix composition, changing signalling events, or damaging the secretory cells due to aberrant intracellular accumulation of secretory proteins. Diseases of aberrant secretion are very common, but despite this, there are few effective therapies. Here we describe ER exit sites (ERES) as key hubs for regulation of the secretory pathway, protein quality control and an integratory hub for signalling within the cell. This review also describes the challenges that will be faced in developing effective therapies, due to the specificity required of potential drug candidates and the crucial need to respect the fine equilibrium of the pathway. The development of novel tools is moving forward, and we can also use these tools to build our understanding of the acute regulation of ERES and protein trafficking. Here we review ERES regulation in context as a therapeutic strategy

The effect of whole grain wheat sourdough bread consumption on serum lipids in healthy normoglycemic/normoinsulinemic and hyperglycemic/hyperinsulinemic adults depends on presence of the APOE E3/E3 genotype: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Epidemiological studies associate consumption of whole grain foods, including breads, with reduced cardiovascular disease (CVD) risk; however, few studies have compared wheat whole grains with wheat refined grains.</p> <p>Methods</p> <p>This study investigated effects of 6-week consumption of whole grain wheat sourdough bread in comparison to white bread on fasting serum lipids in normoglycemic/normoinsulinemic (NGI; n = 14) and hyperglycemic/hyperinsulinemic (HGI; n = 14) adults. The influence of single-nucleotide polymorphisms, 3 within the <it>APOE </it>gene (E2, E3, E4) and 2 within the hepatic lipase gene promoter (<it>LIPC </it>-514C>T, LIPC -250G>A) were considered.</p> <p>Results</p> <p>At baseline, HGI participants had significantly higher body weight, waist circumference, body fat, and fasted glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), glucagon, triacylglycerols (TAG) and TAG:HDL-cholesterol, compared to NGI participants; however, none of these in addition to none of the other serum lipids, differed between bread treatments, within either participant group. For participants with the <it>APOE </it>E3/E3 genotype, LDL-cholesterol (<it>P </it>= 0.02) increased in the NGI group (n = 7), and TAG (<it>P </it>= 0.03) and TAG:HDL-cholesterol (<it>P </it>= 0.04) increased in the HGI group (n = 10), following consumption of whole grain wheat sourdough compared to white bread.</p> <p>Conclusions</p> <p>In summary, 6-week consumption of whole grain wheat sourdough bread did not significantly modulate serum lipids in NGI or HGI adults; however, it significantly increased LDL-cholesterol, TAG and TAG:HDL-cholesterol in participants with the <it>APOE </it>E3/E3 genotype. These data add to limited literature comparing wheat whole grains to wheat refined grains on CVD risk and highlight the need to consider genetic variation in relation to lipoprotein lipid content and CVD risk.</p

Primary hemiarthroplasty for treatment of proximal humeral fractures

Background: Primary hemiarthroplasty of the shoulder is used to treat complex proximal humeral fractures, although the reported functional results following this method of treatment have varied widely. The aim of this study was to prospectively assess the prosthetic survival and functional outcomes in a large series of patients treated with shoulder hemiarthroplasty for a proximal humeral fracture. By determining the factors that affected the outcome, we also aimed to produce models that could be used clinically to estimate the functional outcome at one year following surgery.Methods: A thirteen-year observational cohort study of 163 consecutive patients treated with hemiarthroplasty for a proximal humeral fracture was performed. Twenty-five patients died or were lost to follow-up in the first year after treatment, leaving 138 patients who had assessment of shoulder function with use of the modified Constant score at one year postinjury.Results: The overall rate of prosthetic survival was 96.9% at one year, 95.3% at five years, and 93.9% at ten years. The overall median modified Constant score was 64 points at one year, with a typically good score for pain relief (median, 15 points) and poorer scores, with a greater scatter of values, for function (median, 12 points), range of motion (median, 24 points), and muscle power (median, 14 points). Of the factors that were assessed immediately after the injury, only patient age, the presence of a neurological deficit, tobacco usage, and alcohol consumption were significantly predictive of the one-year Constant score (p &lt; 0.05). Of the factors that were assessed at six weeks postinjury, those that predicted the one-year Constant score included the age of the patient, the presence of a persistent neurological deficit, the need for an early reoperation, the degree of displacement of the prosthetic head from the central axis of the glenoid seen radiographically, and the degree of displacement of the tuberosities seen radiographically.Conclusions: Primary shoulder hemiarthroplasty performed for the treatment of a proximal humeral fracture in medically fit and cooperative adults is associated with satisfactory prosthetic survival at an average of 6.3 years. Although the shoulder is usually free of pain following this procedure, the overall functional result, in terms of range of motion, function, and power, at one year varies. A good functional outcome can be anticipated for a younger individual who has no preoperative neurological deficit, no postoperative complications, and a satisfactory radiographic appearance of the shoulder at six weeks. The results are poorer in the larger group of elderly patients who undergo this procedure, especially if they have a neurological deficit, a postoperative complication requiring a reoperation, or an eccentrically located prosthesis with retracted tuberosities.<br /

Maternal Dietary Patterns during Pregnancy Are Associated with Child Growth in the First 3 Years of Life

Background: Child obesity is a major problem in the United States. Identifying early-life risk factors is necessary for prevention. Maternal diet during pregnancy is a primary source of fetal energy and might influence risk of child obesity

Maternal Dietary Patterns are Associated with Lower Levels of Cardiometabolic Markers during Pregnancy

Elevated levels of cardiometabolic markers are characteristic of normal pregnancy; however, insulin resistance and increased glucose, triglyceride, and cholesterol levels can adversely influence maternal and child health. Diet is a modifiable behavior that could have significant impact on maternal cardiometabolic levels during pregnancy. We investigated the association between dietary patterns and cardiometabolic markers (glucose, insulin, insulin resistance (HOMA-IR), triglycerides, and cholesterol) during pregnancy