The component polypeptide chains of bovine insulin nucleate or inhibit aggregation of the parent protein in a conformation-dependent manner

Amyloid fibrils are typically rigid, unbrariched structures with diameters of similar to 10 nm and lengths up to several micrometres, and are associated with more than 20 diseases including Alzheimer's disease and type II diabetes. Insulin is a small, predominantly alpha-helical protein consisting of 51 residues in two disulfide-linked polypeptide chains that readily assembles into amyloid fibrils under conditions of low PH and elevated temperature. We demonstrate here that both the A-chain and the B-chain of insulin are capable of forming amyloid fibrils in isolation under similar conditions, with fibrillar morphologies that differ from those composed of intact insulin. Both the A-chain and B-chain fibrils were found to be able to cross-seed the fibrillization of the parent protein, although these reactions were substantially less efficient than self-seeding with fibrils composed of full-length insulin. In both cases, the cross-seeded fibrils were morphologically distinct from the seeding, material, but shared common characteristics with typical insulin fibrils, including a very similar helical repeat. The broader distribution of heights of the cross-seeded fibrils compared to typical insulin fibrils, however, indicates that their underling protofilament hierarchy may be subtly different. In addition, and remarkably in view of this seeding behavior, the soluble forms of the A-chain and B-chain peptides were found to be capable of inhibiting insulin fibril formation. Studies using mass spectrometry suggest that this behavior might be attributable to complex formation between insulin and the A-chain and B-chain peptides. The finding that the same chemical form of a polypeptide chain in different physical states can either stimulate or inhibit the conversion of a protein into amyloid fibrils sheds new light on the mechanisms underlying fibril formation, fibril strain propagation and amyloid disease initiation and progression. (c) 2006 Elsevier Ltd. All rights reserved.

Suttonella ornithocola sp nov., from birds of the tit families, and emended description of the genus Suttonella

Phenotypic and phylogenetic studies were performed on three strains of Gram-negative, rod-shaped organisms recovered from dead birds of the tit families (blue tit, coal tit and long-tailed tit). Morphological, cultural and biochemical studies indicated that the organisms were related to the family Cardiobacteriaceae in the gamma-subclass of the Proteobacteria. Comparative 16S rRNA gene sequencing studies confirmed these findings and demonstrated that the bacterium represents a hitherto unknown subline within this family. The closest phylogenetic relative of the strains isolated from the birds was found to be Suttonella indologenes, although a sequence divergence of approximately 5 % demonstrated that the unknown bacterium represented a novel species. On the basis of the results of the phylogenetic analysis and phenotypic criteria, it is proposed that the bacteria recovered from the diseased birds represent a novel species, Suttonella ornithocola sp. nov., with strain B6/99/2(T) (=CCUG 49457(T)=NCTC 13337(T)) as the type strain.

Self-, parent-report and interview measures of obsessive-compulsive disorder in children and adolescents

Self-report measures of obsessive-compulsive disorder (OCD) in children and adolescents are needed for practical evaluation of severity and treatment response. We compared the self- and parent-report Obsessional Compulsive Inventory Revised (CHOCI-R) to the interview-based Child Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) in a clinical sample of 285 children and adolescents with OCD. Classical test theory and item-response theory were applied to compare the instruments. The self- and parent-report CHOCI-R had good internal consistency and were strongly related to each other. The self- and parent-report CHOCI-R severity scores correlated with the CY-BOCS (Pearson's r 0.55 and 0.45 respectively). The CY-BOCS discriminated better at the severe end of the spectrum. The CHOCI-R provided better discrimination in the mild to moderate range. The time-efficient self- and parent-report alternatives will enable routine measurement of OCD severity in clinical practice. Estimates of equivalent summed scores are provided to facilitate comparison. (c) 2007 Elsevier Ltd. All rights reserved.

Williams Syndrome: the extent of agreement between parent and self report of psychological difficulties

Background and Objectives: People with Williams syndrome (WS) have been reported by their carers to have problems with attention, anxiety and social relationships. People with WS have been shown to report their anxieties. This study extends our knowledge of how people with WS see themselves in terms of behaviour and social relationships. Methods: A survey using self and parent report forms of the Strengths and Difficulties Questionnaire. Results: Both parents and individuals with WS (N = 31) reported difficulties in emotional disorder and hyperactivity symptoms and strengths in prosocial behaviours such as altruism and empathy. They disagreed about peer problems. Conclusions: People with WS understand some but not all of their difficulties. In particular they fail to recognize their social difficulties which may lead them to be vulnerable to exploitation.

Analysis of disputed single-parent/child and sibling relationships using 16 STR loci

This study describes the validation of short tandem repeat (STR) systems for the resolution of cases of disputed parentage where only a single parent is available for testing or where the claimed relationship of both parents is in doubt and also cases where sibship must be tested. Three separate multiplex systems the Second Generation Multiplex, Powerplex 1.2 and FFFL have been employed, giving a total of 16 STR loci. Both empirical and theoretical approaches to the validation have been adopted. Appropriate equations have been derived to calculate likelihood ratios for different relationships, incorporating a correction for subpopulation effects. An F(ST) point estimate of 1% has been applied throughout. Empirically, 101 cases of alleged father, alleged mother and child where analysed using six SLP systems and also using the three multiplex STR systems. Of the 202 relationships tested, 197 were independently resolved by both systems, providing either clear evidence of non-parentage or strong support for the relationship.

Cumulant-based deconvolution and identification: several new families of linear equations

This paper presents several new families of cumulant-based linear equations with respect to the inverse filter coefficients for deconvolution (equalisation) and identification of nonminimum phase systems. Based on noncausal autoregressive (AR) modeling of the output signals and three theorems, these equations are derived for the cases of 2nd-, 3rd and 4th-order cumulants, respectively, and can be expressed as identical or similar forms. The algorithms constructed from these equations are simpler in form, but can offer more accurate results than the existing methods. Since the inverse filter coefficients are simply the solution of a set of linear equations, their uniqueness can normally be guaranteed. Simulations are presented for the cases of skewed series, unskewed continuous series and unskewed discrete series. The results of these simulations confirm the feasibility and efficiency of the algorithms.

Maternal affective disorder and children’s representation of their families

Children’s perceptions of family relationship are related to their later emotional and social adjustment. This is of particular relevance in the context of family stressors such as maternal affective disorder. This study investigated the effects of maternal postnatal depression and anxiety on children’s family representations. In our sample of postnatally depressed mothers we also explored marital conflict as mediator between maternal psychopathology and children’s representations. Family drawings of 235 4–5 year-old children (93 control, 53 depressed and 89 anxious) were examined. When compared to controls, children of depressed, but not of anxious mothers, were more likely to draw themselves as less prominent than other family members and to represent a dysfunctional family, less likely to represent themselves with a happy face and showed a greater tendency of drawing bizarre pictures. Marital conflict mediated the association between maternal depression and dysfunctionality in drawings.

Evolutionary genomics of the Fox genes: origin of gene families and the ancestry of gene clusters

Over the past decade genomic approaches have begun to revolutionise the study of animal diversity. In particular, genome sequencing programmes have spread beyond the traditional model species to encompass an increasing diversity of animals from many different phyla, as well as unicellular eukaryotes that are closely related to the animals. Whole genome sequences allow researchers to establish, with reasonable confidence, the full complement of any particular family of genes in a genome. Comparison of gene complements from appropriate genomes can reveal the evolutionary history of gene families, indicating when both gene diversification and gene loss have occurred. More than that, however, assembled genomes allow the genomic environment in which individual genes are found to be analysed and compared between species. This can reveal how gene diversification occurred. Here, we focus on the Fox genes, drawing from multiple animal genomes to develop an evolutionary framework explaining the timing and mechanism of origin of the diversity of animal Fox genes. Ancient linkages between genes are a prominent feature of the Fox genes, depicting a history of gene clusters, some of which may be relevant to understanding Fox gene function.

Poverty, HIV, and barriers to education: street children's experiences in Tanzania

This article discusses the links between poverty, HIV/AIDS, and barriers to education, based on the first-hand experiences of ‘street children’ in northern Tanzania. Within the context of national levels of poverty, ‘cost-sharing’ in health and education sectors, and the AIDS epidemic, poor families in Tanzania are under considerable pressure, and increasing numbers of girls and boys are consequently seeking a living independently on the streets of towns and cities. My research with street children shows that some children orphaned by AIDS are subject to rejection and exploitation by the extended family after the death of their parent(s). They are exposed to considerable risks of abuse, sexual violence and HIV within the street environment. Here, I discuss the links between poverty, HIV and barriers to education, which compound young people’s vulnerability, and offer some policy recommendations in response to the young people’s experiences.