Summary of experiments.

(I) General comments and highlights. (II) Scald: Fungicidal control. 82BA21, 82E18, 82MT19, 82WH23, 82WH23. (III) Scald: Opportunity trial on fungicidal control. 82AL85, 82BA22, 82MT20. (IV) Scald: Epidemic in segregating populations. (V) Scald: Host reaction in hill plots and single plants. 82MT21, 82BA23, (VI) Scald: Seeding rate in evaluating cultivars for resistance. 82MT22, (VII) Net-type net blotch: Screening fungicides. 82BA25, 82KA25. (VIII) Net-type net blotch: Reactions in single plants and hill plots. 82A3, 82BA26. (IX) Spot-type net blotch: Screening fungicides. 82C16. (X) Spot-type net blotch: Potential yield losses. 82C14, 82C15. (XI) Effect of simulated stubble mulching on disease and yield. 82BA36, 82BA35, 82C32, 82MT43,82N27. (XII) Maximising barley yield: Fungicide x growth regulator x cultivar. 82E19,. (XIII) Maximising barley yield: Fungicide x cultivar x nitrogen. (XIV) Variation in pathogenicity of scald, net blotch and powdery mildew. (XV) Unidentified leaf spot on forrest barley. (XVI) Opportunity trial on powdery mildew

A creature with a hundred waggly tails: intrinsically disordered proteins in the ribosome

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.Intrinsic disorder (i.e., lack of a unique 3-D structure) is a common phenomenon, and many biologically active proteins are disordered as a whole, or contain long disordered regions. These intrinsically disordered proteins/regions constitute a significant part of all proteomes, and their functional repertoire is complementary to functions of ordered proteins. In fact, intrinsic disorder represents an important driving force for many specific functions. An illustrative example of such disorder-centric functional class is RNA-binding proteins. In this study, we present the results of comprehensive bioinformatics analyses of the abundance and roles of intrinsic disorder in 3,411 ribosomal proteins from 32 species. We show that many ribosomal proteins are intrinsically disordered or hybrid proteins that contain ordered and disordered domains. Predicted globular domains of many ribosomal proteins contain noticeable regions of intrinsic disorder. We also show that disorder in ribosomal proteins has different characteristics compared to other proteins that interact with RNA and DNA including overall abundance, evolutionary conservation, and involvement in protein–protein interactions. Furthermore, intrinsic disorder is not only abundant in the ribosomal proteins, but we demonstrate that it is absolutely necessary for their various functions

A minimum income standard for Britain : What people think

A minimum income standard, based on what people said is needed to achieve an acceptable standard of living in Britain today. While politicians from all parties are committed to tackling relative poverty, the debates lack a robust definition of a minimum income standard (MIS), below which people’s incomes should not fall. This study devised a minimum income standard for Britain based on what members of the public said, and shows the cost of covering basic goods and services for different household types. The project blends the best elements of the two main methods that have been used to develop budget standards in Britain in recent years. It reconciles the views of experts with those of ordinary people, allowing budgets based on social consensus to be tested against expert knowledge and research. As such, the MIS represents a new and important tool for informing social policy in order to promote fairness and well-being in Britain

Protein disorder in the human diseasome: unfoldomics of human genetic diseases

Background Intrinsically disordered proteins lack stable structure under physiological conditions, yet carry out many crucial biological functions, especially functions associated with regulation, recognition, signaling and control. Recently, human genetic diseases and related genes were organized into a bipartite graph (Goh KI, Cusick ME, Valle D, Childs B, Vidal M, et al. (2007) The human disease network. Proc Natl Acad Sci U S A 104: 8685–8690). This diseasome network revealed several significant features such as the common genetic origin of many diseases. Methods and findings We analyzed the abundance of intrinsic disorder in these diseasome network proteins by means of several prediction algorithms, and we analyzed the functional repertoires of these proteins based on prior studies relating disorder to function. Our analyses revealed that (i) Intrinsic disorder is common in proteins associated with many human genetic diseases; (ii) Different disease classes vary in the IDP contents of their associated proteins; (iii) Molecular recognition features, which are relatively short loosely structured protein regions within mostly disordered sequences and which gain structure upon binding to partners, are common in the diseasome, and their abundance correlates with the intrinsic disorder level; (iv) Some disease classes have a significant fraction of genes affected by alternative splicing, and the alternatively spliced regions in the corresponding proteins are predicted to be highly disordered; and (v) Correlations were found among the various diseasome graph-related properties and intrinsic disorder. Conclusion These observations provide the basis for the construction of the human-genetic-disease-associated unfoldome

Can oral infection be a risk factor for Alzheimer’s disease?

Alzheimer’s disease (AD) is a scourge of longevity that will drain enormous resources from public health budgets in the future. Currently, there is no diagnostic biomarker and/or treatment for this most common form of dementia in humans. AD can be of early familial-onset or sporadic with a late-onset. Apart from the two main hallmarks, amyloid-beta and neurofibrillary tangles, inflammation is a characteristic feature of AD neuropathology. Inflammation may be caused by a local central nervous system insult and/or by peripheral infections. Numerous microorganisms are suspected in AD brains ranging from bacteria (mainly oral and non-oral Treponema species), viruses (Herpes simplex type I) and yeasts (Candida species). A causal relationship between periodontal pathogens/non-oral Treponema species of bacteria has been proposed via the amyloid-beta and inflammatory links. Periodontitis constitutes a peripheral oral infection that can provide the brain with intact bacteria and virulence factors and inflammatory mediators due to daily, transient bacteraemias. If and when genetic risk factors meet environmental risk factors in the brain, disease is expressed, in which neurocognition may be impacted, leading to the development of dementia. To achieve the goal of finding a diagnostic biomarker and possible prophylactic treatment for AD, there is an initial need to solve the etiological puzzle contributing to its pathogenesis. This review therefore addresses oral infection as the plausible aetiology of late onset AD (LOAD)

Validation of the Wider Outcomes Survey for Teachers (WOST): a measure for assessing the behaviour, relationships and exposure to bullying of children and young people with special educational needs and disabilities (SEND)

The Wider Outcomes Survey for Teachers (WOST) is a teacher informant-report questionnaire developed to aid the assessment of behaviour difficulties, quality of relationships and exposure to bullying among students identified with special educational needs and disabilities (SEND). This study examines the psychometric properties of the WOST in a validation sample representing 6164 students with SEND (mean age 12 years) drawn from 481 primary and secondary schools across England. Results showed favourable internal consistency using Cronbach's alpha and acceptable model fit using confirmatory factor analysis, both of which were invariant to broad categorisations of SEND. Practical utility and construct validity were also established by testing two theoretically derived hypotheses. The measure is therefore tentatively supported as a useful tool for assessing the wider outcomes of students with SEND

Concurrent adaptation to opposing visual displacements during an alternating movement.

It has been suggested that, during tasks in which subjects are exposed to a visual rotation of cursor feedback, alternating bimanual adaptation to opposing rotations is as rapid as unimanual adaptation to a single rotation (Bock et al. in Exp Brain Res 162:513–519, 2005). However, that experiment did not test strict alternation of the limbs but short alternate blocks of trials. We have therefore tested adaptation under alternate left/right hand movement with opposing rotations. It was clear that the left and right hand, within the alternating conditions, learnt to adapt to the opposing displacements at a similar rate suggesting that two adaptive states were formed concurrently. We suggest that the separate limbs are used as contextual cues to switch between the relevant adaptive states. However, we found that during online correction the alternating conditions had a significantly slower rate of adaptation in comparison to the unimanual conditions. Control conditions indicate that the results are not directly due the alternation between limbs or to the constant switching of vision between the two eyes. The negative interference may originate from the requirement to dissociate the visual information of these two alternating displacements to allow online control of the two arms

Flexible nets: disorder and induced fit in the associations of p53 and 14-3-3 with their partners

Background: Proteins are involved in many interactions with other proteins leading to networks that regulate and control a wide variety of physiological processes. Some of these proteins, called hub proteins or hubs, bind to many different protein partners. Protein intrinsic disorder, via diversity arising from structural plasticity or flexibility, provide a means for hubs to associate with many partners (Dunker AK, Cortese MS, Romero P, Iakoucheva LM, Uversky VN: Flexible Nets: The roles of intrinsic disorder in protein interaction networks. FEBS J 2005, 272:5129-5148). Results: Here we present a detailed examination of two divergent examples: 1) p53, which uses different disordered regions to bind to different partners and which also has several individual disordered regions that each bind to multiple partners, and 2) 14-3-3, which is a structured protein that associates with many different intrinsically disordered partners. For both examples, three-dimensional structures of multiple complexes reveal that the flexibility and plasticity of intrinsically disordered protein regions as well as induced-fit changes in the structured regions are both important for binding diversity. Conclusions: These data support the conjecture that hub proteins often utilize intrinsic disorder to bind to multiple partners and provide detailed information about induced fit in structured regions

Disease-Associated Mutations Disrupt Functionally Important Regions of Intrinsic Protein Disorder

The effects of disease mutations on protein structure and function have been extensively investigated, and many predictors of the functional impact of single amino acid substitutions are publicly available. The majority of these predictors are based on protein structure and evolutionary conservation, following the assumption that disease mutations predominantly affect folded and conserved protein regions. However, the prevalence of the intrinsically disordered proteins (IDPs) and regions (IDRs) in the human proteome together with their lack of fixed structure and low sequence conservation raise a question about the impact of disease mutations in IDRs. Here, we investigate annotated missense disease mutations and show that 21.7% of them are located within such intrinsically disordered regions. We further demonstrate that 20% of disease mutations in IDRs cause local disorder-to-order transitions, which represents a 1.7–2.7 fold increase compared to annotated polymorphisms and neutral evolutionary substitutions, respectively. Secondary structure predictions show elevated rates of transition from helices and strands into loops and vice versa in the disease mutations dataset. Disease disorder-to-order mutations also influence predicted molecular recognition features (MoRFs) more often than the control mutations. The repertoire of disorder-to-order transition mutations is limited, with five most frequent mutations (R→W, R→C, E→K, R→H, R→Q) collectively accounting for 44% of all deleterious disorder-to-order transitions. As a proof of concept, we performed accelerated molecular dynamics simulations on a deleterious disorder-to-order transition mutation of tumor protein p63 and, in agreement with our predictions, observed an increased α-helical propensity of the region harboring the mutation. Our findings highlight the importance of mutations in IDRs and refine the traditional structure-centric view of disease mutations. The results of this study offer a new perspective on the role of mutations in disease, with implications for improving predictors of the functional impact of missense mutations