The amino acid composition of basic proteins of the cell nucleus

Although genetics deals with rather superficial characteristics, such as eye colour and skin colour, it does not follow that only such characteristics come under chromosomal control. Because of the difficulty of crossing individuals from different species, genetical evidence is largely derived from studies of superficial character variations within particular species, and cannot, therefore, be expected to throw much light on the more fundamental aspects of cell function. However, in any biochemical interpretation of genetical control of even superficial cellular characteristics, one could not avoid associating the part played by the genes in controlling these with the control of the wider aspects of cell function. Moreover, the number of characteristics now known to come under genetical control is so large that it seems evident that the only reason why genetical control of fundamental aspects of cell function has not been demonstrated is that genetical studies suffer from the inherent limitations already mentioned.Since the publication of the Stedmans' hypothesis, Dr Stedman and Mr H. Cruft, working in this laboratory, have found that the main histones for which species and cell specificity had been demonstrated, actually consist of two components, distinguishable by different mobilities during electrophoresis. Generally, each main histone has been found to consist of a major component, and a minor component possessing a slower mobility, and these have been designated the 'main component' and the 'slow component' respectively. An account of this work has yet to be published.It seemed possible that this discovery might obscure the significance of the Stedmans' demonstration of species and cell specificity since this had been based on analyses of unfractionated main histones. For example, it could be argued that the differences in amino acid composition observed were due to the presence of different proportions of the two component histones in the different kinds of cell nuclei studied. Thus it became necessary to fractionate several of the main histones into two electrophoretically homogeneous components and to carry out analyses of the pure components with a view to confirming the evidence of cell and species specificity presented in the Stedmans' (1951) publication. In view of the fact that the scope of the Stedmans' analyses was rather limited, the only amino acids estimated quantitatively being arginine and tyrosine, it was also considered necessary to use a method of analysis covering a lamer number of amino acids. This thesis is an account of the development of such a method and its application to the analysis of histones.The work falls naturally into several sections. MacPherson (1946) published details of a method of analysis of the three basic amino acids involving the separation of the basic fraction from whole protein hydrolysates as a preliminary step. The recoveries hes quoted were so good that it was decided to examine this method to see if it could be satisfactorily applied to the analysis of histones. The first section of this work is thus an account of experiments which were carried out using MacPherson's technique in a slightly modified form. It was concluded, as a result of these experiments, that MacPherson's electrodialysis technique was unsuitable for the author's purposes.The subsequent section deals with the development of a method of analysis which is similar to IVacPherson's method in that the basic fraction is separated from the whole hydrolysate preliminary to the estimation of the basic amino acids. But it differs from this method in the important respect that an ion exchange resin, Amberlite IRC -50, is used for the separation of the basic fraction. MacPherson's actual analytical methods have been retained with minor modifications.In Section III there is an account of the application of the method to the analysis of histones. 1 Since the main purpose of the work is the confirmation of the phenomena of the species specificity and cel specificity " i of histones for e lectro p izoretícall y homogeneous histone components, results for the analyses of the main component histones from different types of cells from two different species are presented. In addition, results of a number of analyses of unfractionated main histones, slow component histones, and the protamines salmine and clupeine, have bees. given.Since the scope of the analytical method . developed is still rather limited, some work has been carried out with a view to extending it to include the acidic amino acids. The final section has therefore been devoted to describing a few experiments which were designed to separate the acidic amino acids from composite amino acid solutions using the anion exchanger, Amberlite IR-4B

Adolescent testosterone influences BDNF and TrkB mRNA and neurotrophin–interneuron marker relationships in mammalian frontal cortex

AbstractLate adolescence in males is a period of increased susceptibility for the onset of schizophrenia, coinciding with increased circulating testosterone. The cognitive deficits prevalent in schizophrenia may be related to unhealthy cortical interneurons, which are trophically dependent on brain derived neurotrophic factor. We investigated, under conditions of depleted (monkey and rat) and replaced (rat) testosterone over adolescence, changes in gene expression of cortical BDNF and TrkB transcripts and interneuron markers and the relationships between these mRNAs and circulating testosterone. Testosterone removal by gonadectomy reduced gene expression of some BDNF transcripts in monkey and rat frontal cortices and the BDNF mRNA reduction was prevented by testosterone replacement. In rat, testosterone replacement increased the potential for classical TrkB signalling by increasing the full length to truncated TrkB mRNA ratio, whereas in the monkey cortex, circulating testosterone was negatively correlated with the TrkB full length/truncated mRNA ratio. We did not identify changes in interneuron gene expression in monkey frontal cortex in response to gonadectomy, and in rat, we showed that only somatostatin mRNA was decreased by gonadectomy but not restored by testosterone replacement. We identified complex and possibly species-specific, relationships between BDNF/TrkB gene expression and interneuron marker gene expression that appear to be dependent on the presence of testosterone at adolescence in rat and monkey frontal cortices. Taken together, our findings suggest there are dynamic relationships between BDNF/TrkB and interneuron markers that are dependent on the presence of testosterone but that this may not be a straightforward increase in testosterone leading to changes in BDNF/TrkB that contributes to interneuron health

Design as a Marked Point Process

Although AI systems which support composition using predictive text are well established there are no analogous technologies for mechanical design. Motivated by the vision of a predictive system that interactively suggests features to designer, this paper describes the theory, implementation and assessment of an intelligent system that learns from a family of previous designs and generates inferences using a form of spatial statistics.The formalism presented, models 3D design activity as a `Marked Point Process' that enables the probability of specific features being added at a particular locations to be calculated. Because the resulting probabilities are updated every time a new feature is added the predictions will become more accurate as a design develops. This approach allows the cursor position on a CAD model to implicitly define a spatial focus for every query made to the statistical model. The authors describe the mathematics underlying a statistical model thatamalgamates the frequency of occurrence of the features in the existing designs of a product family.Having established the theoretical foundations of the work, a generic six step implementation process is described. This process is then illustrated for circular hole features using a statistical model generated from a dataset of hydraulic valves. The paper describes how the positions of each design's extracted hole features can be homogenized through rotation and scaling. Results suggest that within generic part families (i.e. designs with common structure) a marked point process can be effective at predicting incremental steps in the development of new designs

Using molecular networking for microbial secondary metabolite bioprospecting

The oceans represent an understudied resource for the isolation of bacteria with the potential to produce novel secondary metabolites. In particular, actinomyces are well known to produce chemically diverse metabolites with a wide range of biological activities. This study characterised spore-forming bacteria from both Scottish and Antarctic sediments to assess the influence of isolation location on secondary metabolite production. Due to the selective isolation method used, all 85 isolates belonged to the phyla Firmicutes and Actinobacteria, with the majority of isolates belonging to the genera Bacillus and Streptomyces. Based on morphology, thirty-eight isolates were chosen for chemical investigation. Molecular networking based on chemical profiles (HR-MS/MS) of fermentation extracts was used to compare complex metabolite extracts. The results revealed 40% and 42% of parent ions were produced by Antarctic and Scottish isolated bacteria, respectively, and only 8% of networked metabolites were shared between these locations, implying a high degree of biogeographic influence upon secondary metabolite production. The resulting molecular network contained over 3500 parent ions with a mass range of m/z 149-2558 illustrating the wealth of metabolites produced. Furthermore, seven fermentation extracts showed bioactivity against epithelial colon adenocarcinoma cells, demonstrating the potential for the discovery of novel bioactive compounds from these understudied locations

Common design structures and substitutable feature discovery in CAD databases

It has been widely reported that the reuse of previously created components, or features, in new engineering designs will improve the efficiency of a company’s product development process. Although the reuse of engineering components has established metrics and methodologies, the reuse of specific design features (e.g. stiffening ribs, hole patterns or lubrication grooves, etc.) has received less attention in the literature. Typically, researchers have reported approaches to partial design reuse that identify patterns predominately in terms of geometrically similar shapes (i.e. a set of features) whose elements are adjacent, cohesive, and decoupled from the overall form of a component. In contrast, this paper defines a common design structure (CDS) as collections of frequently occurring features (e.g. holes) with common parametric values (e.g. diameters) in a CAD database (irrespective of their locations or spatial connectivity between other features on a component). By exploiting the established data-mining technology of association rules and item-sets the authors show how CDSs can be efficiently computed for hundreds of 3D CAD models. A case study, with hole data extracted from a publicly available dataset of hydraulic valves, is presented to illustrate how item-sets associated with CDS can be computed and used to support predictive design by identifying potentially ‘substitutable features’ during an interactive design process. This is done using a combination of association rules and geometric compatibility checks to ensure the system’s suggestion are implementable. The use of the Kullback–Leibler divergence to assess the degree of similarity between components is identified as a crucial step in the process of identifying the “best” suggestions. The results illustrate how the prototype implementation successfully mines the CDSs and identifies substitutable hole features in a dataset of industrial valve designs

Assessment of Predictive Probability Models for Effective Mechanical Design Feature Reuse

This research envisages an automated system to inform engineers when opportunities occur to use existing features or configurations during the development of new products. Such a system could be termed a `predictive CAD system' because it would be able to suggest feature choices that follow patterns established in existing products. The predictive CAD literature largely focuses on predicting components for assemblies using 3D solid models. In contrast,this research work focuses on feature-based predictive CAD system using B-rep models. This paper investigates the performance of predictive models that could enable the creation of such an intelligent CAD system by assessing three different methods to support inference: sequential, machine learning or probabilistic methods using N-Grams, Neural Networks (NN) and Bayesian Networks (BN) as representative of these methods.After defining the functional properties that characterise a predictive design system a generic development methodology is presented. The methodology is used to carry out a systematic assessment of the relative performance of three methods each used to predict the diameter value of the next hole and boss feature type being added during the design of a hydraulic valve body.Evaluating predictive performance; providing five recommendations (k=5) for hole or boss features as a new design was developed, recall@k increased from around 30% to 50% and precision@ k from around 50% to 70% as one to three features were added. The results indicate that the Bayesian and Neural Network models perform better than those using N-Grams. The practical impact of this contribution is assessed using a prototype (implemented as an extension to a commercial CAD system) by engineers whose comments defined an agenda for ongoing research in this area

Influences of Forest Structure, Climate and Species Composition on Tree Mortality across the Eastern US

Few studies have quantified regional variation in tree mortality, or explored whether species compositional changes or within-species variation are responsible for regional patterns, despite the fact that mortality has direct effects on the dynamics of woody biomass, species composition, stand structure, wood production and forest response to climate change. Using Bayesian analysis of over 430,000 tree records from a large eastern US forest database we characterised tree mortality as a function of climate, soils, species and size (stem diameter). We found (1) mortality is U-shaped vs. stem diameter for all 21 species examined; (2) mortality is hump-shaped vs. plot basal area for most species; (3) geographical variation in mortality is substantial, and correlated with several environmental factors; and (4) individual species vary substantially from the combined average in the nature and magnitude of their mortality responses to environmental variation. Regional variation in mortality is therefore the product of variation in species composition combined with highly varied mortality-environment correlations within species. The results imply that variation in mortality is a crucial part of variation in the forest carbon cycle, such that including this variation in models of the global carbon cycle could significantly narrow uncertainty in climate change predictions