Planning methods for agriculture in less-developed countries.

This paper will consider agricultural planning methodology under four heads. Firstly, the major features and problems of t he typical agricultural sector in a less- developed country are discussed with particular reference to the economic planning process, Secondly , standard planning procedures for the inter-sectoral allocation of resources are assessed from the point of view of their feasibility and accuracy for the agricultural sector . The identification of alternative strategies for agricultural development is then discussed briefly and finally the main features of a systematic planning procedure for the agricultural sector are presented

Why genes overlap in viruses

The genomes of most virus species have overlapping genes\u2014two or more proteins coded for by the same nucleotide sequence. Several explanations have been proposed for the evolution of this phenomenon, and we test these by comparing the amount of gene overlap in all known virus species. We conclude that gene overlap is unlikely to have evolved as a way of compressing the genome in response to the harmful effect of mutation because RNA viruses, despite having generally higher mutation rates, have less gene overlap on average than DNA viruses of comparable genome length. However, we do find a negative relationship between overlap proportion and genome length among viruses with icosahedral capsids, but not among those with other capsid types that we consider easier to enlarge in size. Our interpretation is that a physical constraint on genome length by the capsid has led to gene overlap evolving as a mechanism for producing more proteins from the same genome length. We consider that these patterns cannot be explained by other factors, namely the possible roles of overlap in transcription regulation, generating more divergent proteins and the relationship between gene length and genome length

Discovery of Novel Biomarkers for Alzheimer's Disease from Blood

Blood-based biomarkers for Alzheimer’s disease would be very valuable because blood is a more accessible biofluid and is suitable for repeated sampling. However, currently there are no robust and reliable blood-based biomarkers for practical diagnosis. In this study we used a knowledge-based protein feature pool and two novel support vector machine embedded feature selection methods to find panels consisting of two and three biomarkers. We validated these biomarker sets using another serum cohort and an RNA profile cohort from the brain. Our panels included the proteins ECH1, NHLRC2, HOXB7, FN1, ERBB2, and SLC6A13 and demonstrated promising sensitivity (&gt;87%), specificity (&gt;91%), and accuracy (&gt;89%).</jats:p

Integrated genomic approaches identify major pathways and upstream regulators in late onset Alzheimer's disease.

Previous studies have evaluated gene expression in Alzheimer's disease (AD) brains to identify mechanistic processes, but have been limited by the size of the datasets studied. Here we have implemented a novel meta-analysis approach to identify differentially expressed genes (DEGs) in published datasets comprising 450 late onset AD (LOAD) brains and 212 controls. We found 3124 DEGs, many of which were highly correlated with Braak stage and cerebral atrophy. Pathway Analysis revealed the most perturbed pathways to be (a) nitric oxide and reactive oxygen species in macrophages (NOROS), (b) NFkB and (c) mitochondrial dysfunction. NOROS was also up-regulated, and mitochondrial dysfunction down-regulated, in healthy ageing subjects. Upstream regulator analysis predicted the TLR4 ligands, STAT3 and NFKBIA, for activated pathways and RICTOR for mitochondrial genes. Protein-protein interaction network analysis emphasised the role of NFKB; identified a key interaction of CLU with complement; and linked TYROBP, TREM2 and DOK3 to modulation of LPS signalling through TLR4 and to phosphatidylinositol metabolism. We suggest that NEUROD6, ZCCHC17, PPEF1 and MANBAL are potentially implicated in LOAD, with predicted links to calcium signalling and protein mannosylation. Our study demonstrates a highly injurious combination of TLR4-mediated NFKB signalling, NOROS inflammatory pathway activation, and mitochondrial dysfunction in LOAD

Correcting errors in synthetic DNA through consensus shuffling

Although efficient methods exist to assemble synthetic oligonucleotides into genes and genomes, these suffer from the presence of 1–3 random errors/kb of DNA. Here, we introduce a new method termed consensus shuffling and demonstrate its use to significantly reduce random errors in synthetic DNA. In this method, errors are revealed as mismatches by re-hybridization of the population. The DNA is fragmented, and mismatched fragments are removed upon binding to an immobilized mismatch binding protein (MutS). PCR assembly of the remaining fragments yields a new population of full-length sequences enriched for the consensus sequence of the input population. We show that two iterations of consensus shuffling improved a population of synthetic green fluorescent protein (GFPuv) clones from ∼60 to >90% fluorescent, and decreased errors 3.5- to 4.3-fold to final values of ∼1 error per 3500 bp. In addition, two iterations of consensus shuffling corrected a population of GFPuv clones where all members were non-functional, to a population where 82% of clones were fluorescent. Consensus shuffling should facilitate the rapid and accurate synthesis of long DNA sequences

Bathing adaptations in the homes of older adults (BATH-OUT): protocol for a feasibility randomised controlled trial (RCT)

Introduction The Care Act 2014 has placed a responsibility on local authorities in England to provide services that prevent deterioration and minimise the use of other health and social care services. Housing adaptations have been identified as 1 of the 10 most promising prevention services for older adults, with bathing adaptations being the most requested. However, many local authorities have lengthy waiting times which may increase costs, reduce effectiveness and reduce the preventive effect. There is no robust evidence of the effect of these adaptations on: health, well-being and functional ability. Methods and analysis This is a feasibility randomised controlled trial (RCT) with nested qualitative interview study. The RCT will recruit between 40 and 60 people who have been referred for an accessible showering facility, and their carers, from 1 local authority in England. They will be randomised to either usual adaptations (∼3-month wait) or immediate adaptations (no wait). The primary outcome is the feasibility of conducting a powered study. The outcomes assessed will be: health and social care-related quality of life, independence in activities of daily living and bathing, falls and use of health and social care services. Outcomes will be assessed at 3 and 6 months. Preliminary health economic feasibility will be established. Ethics and dissemination Favourable ethical opinion was provided by the Social Care Research Ethics Committee (reference number 16/IEC08/0017). The results of this study will lay the foundations for a further powered study. This would investigate the effect of bathing adaptations on quality of life and whether increased waiting times are associated with poorer outcomes and increased costs. The results have further potential to inform trials of other housing or social care interventions using the novel waiting list control method. Dissemination will include peer-reviewed publications and presentations at national and international conferences. Trial registration number ISRCTN14876332; Pre-results

Learning from the early adopters: developing the digital practitioner

This paper explores how Sharpe and Beetham’s Digital Literacies Framework which was derived to model students’ digital literacies, can be applied to lecturers’ digital literacy practices. Data from a small-scale phenomenological study of higher education lecturers who used Web 2.0 in their teaching and learning practices are used to examine if this pyramid model represents their motivations for adopting technology-enhanced learning in their pedagogic practices. The paper argues that whilst Sharpe and Beetham’s model has utility in many regards, these lecturers were mainly motivated by the desire to achieve their pedagogic goals rather than by a desire to become a digital practitioner

Nutritional factors and gender influence age-related DNA methylation in the human rectal mucosa

Aberrant methylation of CpG islands (CGI) occurs in many genes expressed in colonic epithelial cells, and may contribute to the dysregulation of signalling pathways associated with carcinogenesis. This cross-sectional study assessed the relative importance of age, nutritional exposures and other environmental factors in the development of CGI methylation. Rectal biopsies were obtained from 185 individuals (84 male, 101 female) shown to be free of colorectal disease, and for whom measurements of age, body size, nutritional status and blood cell counts were available. We used quantitative DNA methylation analysis combined with multivariate modelling to investigate the relationships between nutritional, anthropometric and metabolic factors and the CGI methylation of 11 genes, together with LINE-1 as an index of global DNA methylation. Age was a consistent predictor of CGI methylation for 9/11 genes but significant positive associations with folate status and negative associations with vitamin D and selenium status were also identified for several genes. There was evidence for positive associations with blood monocyte levels and anthropometric factors for some genes. In general, CGI methylation was higher in males than in females and differential effects of age and other factors on methylation in males and females were identified. In conclusion, levels of age-related CGI methylation in the healthy human rectal mucosa are influenced by gender, the availability of folate, vitamin D and selenium, and perhaps by factors related to systemic inflammatio

Systematic Analysis and Biomarker Study for Alzheimer's Disease.

Revealing the relationship between dysfunctional genes in blood and brain tissues from patients with Alzheimer's Disease (AD) will help us to understand the pathology of this disease. In this study, we conducted the first such large systematic analysis to identify differentially expressed genes (DEGs) in blood samples from 245 AD cases, 143 mild cognitive impairment (MCI) cases, and 182 healthy control subjects, and then compare these with DEGs in brain samples. We evaluated our findings using two independent AD blood datasets and performed a gene-based genome-wide association study to identify potential novel risk genes. We identified 789 and 998 DEGs common to both blood and brain of AD and MCI subjects respectively, over 77% of which had the same regulation directions across tissues and disease status, including the known ABCA7, and the novel TYK2 and TCIRG1. A machine learning classification model containing NDUFA1, MRPL51, and RPL36AL, implicating mitochondrial and ribosomal function, was discovered which discriminated between AD patients and controls with 85.9% of area under the curve and 78.1% accuracy (sensitivity = 77.6%, specificity = 78.9%). Moreover, our findings strongly suggest that mitochondrial dysfunction, NF-κB signalling and iNOS signalling are important dysregulated pathways in AD pathogenesis