Myelin basic protein peptide 45–89 induces the release of nitric oxide from microglial cells.

Continuous (24 h) exposure of mixed oligodendrocyte/microglial cells to peptides 45–89 derived from citrullinated C8 isoforms of myelin basic protein (MBP) induces cell death. In contrast, MBP-C8 at the same molecular concentration is not toxic to oligodendrocyte/microglial cells as detected by the MTT test and trypan blue exclusion method. The loss of oligodendrocyte/microglial cells resulted in the release of cytochrome c from mitochondria, suggesting MBP 45–89-induced apoptosis. On the other hand, peptides 45–89 stimulated the secretion of nitric oxide from microglial cells only via induction of iNOS. The addition of peptide 45–89 to the microglial cells led to a decrease of the level of the inhibitory protein IkB, indicating that activation of the transcription factor NF-kB is involved in these processes. We propose that the immunodominant peptide 45–89 induces damage of oligodendrocytes by activation of microglial cells and subsequent generation of nitric oxide, and that this may be the first step in the initiation of autoimmunity

Associated reading skills in children with a history of Specific Language Impairment (SLI)

A large cohort of 200 eleven-year-old children with Specific Language Impairment (SLI) were assessed on basic reading accuracy and on reading comprehension as well as language tasks. Reading skills were examined descriptively and in relation to early language and literacy factors. Using stepwise regression analyses in which age and nonverbal IQ were controlled for, it was found that a single word reading measure taken at 7 years was unsurprisingly a strong predictor of the two different types of reading ability. However, even with this measure included, a receptive syntax task (TROG) entered when reading accuracy score was the DV. Furthermore, a test of expressive syntax/narrative and a receptive syntax task completed at 7 years entered into the model for word reading accuracy. When early reading accuracy was excluded from the analyses, early phonological skills also entered as a predictor of both reading accuracy and comprehension at 11 years. The group of children with a history of SLI were then divided into those with no literacy difficulties at 11 and those with some persisting literacy impairment. Using stepwise logistic regression, and again controlling for IQ and age, 7 years receptive syntax score (but not tests of phonology, expressive vocabulary or expressive syntax/narrative) entered as a positive predictor of membership of the ‘no literacy problems’ group regardless of whether early reading accuracy was controlled for in step one. The findings are discussed in relation to the overlap of SLI and dyslexia and the long term sequelae of language impairment

Nicotinamide, NAD(P)(H), and Methyl-Group Homeostasis Evolved and Became a Determinant of Ageing Diseases: Hypotheses and Lessons from Pellagra

Compartmentalized redox faults are common to ageing diseases. Dietary constituents are catabolized to NAD(H) donating electrons producing proton-based bioenergy in coevolved, cross-species and cross-organ networks. Nicotinamide and NAD deficiency from poor diet or high expenditure causes pellagra, an ageing and dementing disorder with lost robustness to infection and stress. Nicotinamide and stress induce Nicotinamide-N-methyltransferase (NNMT) improving choline retention but consume methyl groups. High NNMT activity is linked to Parkinson's, cancers, and diseases of affluence. Optimising nicotinamide and choline/methyl group availability is important for brain development and increased during our evolution raising metabolic and methylome ceilings through dietary/metabolic symbiotic means but strict energy constraints remain and life-history tradeoffs are the rule. An optimal energy, NAD and methyl group supply, avoiding hypo and hyper-vitaminoses nicotinamide and choline, is important to healthy ageing and avoids utilising double-edged symbionts or uncontrolled autophagy or reversions to fermentation reactions in inflammatory and cancerous tissue that all redistribute NAD(P)(H), but incur high allostatic costs

Narrative skills in adolescents with a history of SLI in relation to non-verbal IQ scores

There is a debate about whether the language of children with primary language disorders and normal cognitive levels is qualitatively different from those with language impairments who have low or borderline non-verbal IQ (NVIQ). As children reach adolescence, this distinction may be even harder to ascertain, especially in naturalistic settings. Narrative may provide a useful, ecologically valid way in which to assess the language ability of adolescents with specific language impairment (SLI) who have intact or lowered NVIQ and to determine whether there is any discernable difference in every day language. Nineteen adolescents with a history of SLI completed two narrative tasks: a story telling condition and a conversational condition. Just under half the group (n = 8) had non-verbal IQs of 85. The remaining 11 had NVIQs in the normal range or above. Four areas of narrative (productivity, syntax, cohesion and performance) were assessed. There were no differences between the groups on standardized tests of language. However, the group with low NVIQ were poorer on most aspects of narrative, suggesting that cognitive level is important, even when language is the primary disorder. The groups showed similar patterns of differences between story telling and conversational narrative. It was concluded that adolescents with a history of SLI and poor cognitive levels have poorer narrative skills than those with normal range NVIQ even though these may not be detected by standardized assessment. Their difficulties present as qualitatively similar to those with normal range NVIQ and narratives appear impoverished rather than inaccurate

Higher education, mature students and employment goals: policies and practices in the UK

This article considers recent policies of Higher Education in the UK, which are aimed at widening participation and meeting the needs of employers. The focus is on the growing population of part-time students, and the implications of policies for this group. The article takes a critical perspective on government policies, using data from a major study of mature part-time students, conducted in two specialist institutions in the UK, a London University college and a distance learning university. Findings from this study throw doubt on the feasibility of determining a priori what kind of study pathway is most conducive for the individual in terms of employment gains and opportunities for upward social mobility. In conclusion, doubts are raised as to whether policies such as those of the present UK government are likely to achieve its aims. Such policies are not unique to the UK, and lessons from this country are relevant to most of the developed world

Secondary gamma-ray production in a coded aperture mask

The application of the coded aperture mask to high energy gamma-ray astronomy will provide the capability of locating a cosmic gamma-ray point source with a precision of a few arc-minutes above 20 MeV. Recent tests using a mask in conjunction with drift chamber detectors have shown that the expected point spread function is achieved over an acceptance cone of 25 deg. A telescope employing this technique differs from a conventional telescope only in that the presence of the mask modifies the radiation field in the vicinity of the detection plane. In addition to reducing the primary photon flux incident on the detector by absorption in the mask elements, the mask will also be a secondary radiator of gamma-rays. The various background components in a CAMTRAC (Coded Aperture Mask Track Chamber) telescope are considered. Monte-Carlo calculations are compared with recent measurements obtained using a prototype instrument in a tagged photon beam line