Plasma enteroglucagon, peptide YY and gastrin in rats deprived of luminal nutrition, and after urogastrone-EGF administration. A proliferative role for PYY in the intestinal epithelium?

Intestinal tissue mass was significantly reduced throughout the gastrointestinal tract (p less than 0.001) of intravenously fed (TPN) rats. Urogastrone-epidermal growth factor, (URO-EGF), reversed these changes. Although plasma enteroglucagon and gastrin levels showed a small increase with URO-EGF, this was far less than the gut tissue weight change, suggesting that it was unlikely that they were involved in modulating the proliferative response of the intestine to URO-EGF. Peptide tyrosine tyrosine (PYY) levels were however significantly increased by URO-EGF, indicating that PYY may possibly have a role in the modulation of intestinal cell proliferation.     

The importance of sequence diversity in the aggregation and evolution of proteins

Incorrect folding of proteins, leading to aggregation and amyloid formation, is associated with a group of highly debilitating medical conditions including Alzheimer's disease and late-onset diabetes. The issue of how unwanted protein association is normally avoided in a living system is particularly significant in the context of the evolution of multidomain proteins, which account for over 70% of all eukaryotic proteins, where the effective local protein concentration in the vicinity of each domain is very high. Here we describe the aggregation kinetics of multidomain protein constructs of immunoglobulin domains and the ability of different homologous domains to aggregate together. We show that aggregation of these proteins is a specific process and that the efficiency of coaggregation between different domains decreases markedly with decreasing sequence identity. Thus, whereas immunoglobulin domains with more than about 70% identity are highly prone to coaggregation, those with less than 30-40% sequence identity do not detectably interact. A bioinformatics analysis of consecutive homologous domains in large multidomain proteins shows that such domains almost exclusively have sequence identities of less than 40%, in other words below the level at which coaggregation is likely to be efficient. We propose that such low sequence identities could have a crucial and general role in safeguarding proteins against misfolding and aggregation.     

Close genetic linkage between X-linked retinitis pigmentosa and a restriction fragment length polymorphism identified by recombinant DNA probe L1.28

Retinitis pigmentosa (RP) is a group of retinal degeneration characterized by progressive visual field loss, night blindness and pigmentary retinopathy. Its prevalence is in the region of 1-2 in 5,000 of the general population, making it one of the commoner causes of blindness in early and middle life. Although 36-48% of RP patients are isolated cases, the remainder show autosomal dominant, autosomal recessive or X-linked modes of inheritance. The X-linked variety ( XLRP ) is found in 14-22% of RP families in the UK. In the present study, X chromosome-specific recombinant DNA probes which can detect restriction fragment length polymorphisms have been used to localize the XLRP gene(s) to a subregion of the X chromosome using linkage analysis. One of the probes, L1.28, has been shown to be closely linked to XLRP in five kindreds, with 95% confidence limits of 0-15 centimorgans (maximum LOD score of 7.89 at a distance of 3 centimorgans). This suggests that the XLRP locus lies on the proximal part of the short arm of the X chromosome. This probe is potentially useful for carrier detection and early diagnosis in about 40% of cases, provided that genetic heterogeneity can be excluded by analysis of further families.     

Forecast covariances in the linear multiregression dynamic model

The linear multiregression dynamic model (LMDM) is a Bayesian dynamic model which preserves any conditional independence and causal structure across a multivariate time series. The conditional independence structure is used to model the multivariate series by separate (conditional) univariate dynamic linear models, where each series has contemporaneous variables as regressors in its model. Calculating the forecast covariance matrix (which is required for calculating forecast variances in the LMDM) is not always straightforward in its current formulation. In this paper we introduce a simple algebraic form for calculating LMDM forecast covariances. Calculation of the covariance between model regression components can also be useful and we shall present a simple algebraic method for calculating these component covariances. In the LMDM formulation, certain pairs of series are constrained to have zero forecast covariance. We shall also introduce a possible method to relax this restriction. Copyright © 2008 John Wiley & Sons, Ltd.     

Integration of mitochondrial gene sequences within the nuclear genome during senescence in a fungus

Cellular senescence in the ascomycete fungus Podospora anserina is associated with the appearance of an altered mitochondrial genome. Discrete mitochondrial DNA sequences are excised and amplified and isolated as multimerically arranged, head-to-tail repetitions. We have referred to the most frequently observed excision/amplification product as alpha-event senDNA. It is a 2.6-kilobase pair (kbp) monomeric unit (see refs 1, 3, 7) and is often found in senescent mitochondria in conjunction with other excision products. At the final stage of senescence these plasmids constitute virtually all of the DNA present in senescent mitochondria; they have replicated to high copy number at the expense of the young native genome. Because P. anserina is characterized by race-specific timing of senescence (that is, a programme of senescence), we have begun to contrast rapidly and slowly senescing races in terms of senDNA. Here we present evidence that young mitochondria of the rapidly senescing race, A+, possess an extremely high copy number of alpha-event senDNA plasmid in contrast to the more slowly senescing races s+ or s-. Moreover, we observe that during senescence the alpha-event senDNA and the beta-event senDNA (a 9.8-kbp monomer) are transposed to the nucleus and integrated into nuclear DNA. These plasmids contain the coding information for subunits I and III (respectively) of the mitochondrial cytochrome c oxidase. This constitutes the first clear evidence for the active mobilization of genetic elements from the mitochondrion to the nucleus.     

Systems Thinking and Systems Practice: Working in the Fifth Dimension

This paper describes how a messy organizational problem was tackled using a systems approach which led to a resolution of the problem and to an improvement in the working relationships of the people involved. The example also shows how people who are not familiar with systems thinking, as such, can quickly be helped to develop a shared systemic view of a complex situation using activity modeling. At a deeper level, the paper also shows how the underlying dynamics of the problem situation was altered as a result of using a cooperative, dialogical working method, leading to an improvement in the quality of service provided by that part of the organization. The paper uses Peter Senge's five disciplines of a learning organization, together with various systems concepts, as a framework for describing how the process of change was brought about through the simultaneous management of task and social processes, leading to both individual and organizational learning.     

Mobilization of a Drosophila transposon in the Caenorhabditis elegans germ line.

Transposons have been enormously useful for genetic analysis in both Drosophila and bacteria. Mutagenic insertions constitute molecular tags that are used to rapidly clone the mutated gene. Such techniques would be especially advantageous in the nematode Caenorhabditis elegans, as the entire sequence of the genome has been determined. Several different types of endogenous transposons are present in C. elegans, and these can be mobilized in mutator strains (reviewed in ref. 1). Unfortunately, use of these native transposons for regulated transposition in C. elegans is limited. First, all strains contain multiple copies of these transposons and thus new insertions do not provide unique tags. Second, mutator strains tend to activate the transposition of several classes of transposons, so that the type of transposon associated with a particular mutation is not known. Here we demonstrate that the Drosophila mariner element Mos1 can be mobilized in C. elegans. First, efficient mobilization of Mos1 is possible in somatic cells. Second, heritable insertions of the transposon can be generated in the germ line. Third, genes that have been mutated by insertion can be rapidly identified using inverse polymerase chain reaction. Fourth, these insertions can subsequently be remobilized to generate deletion and frameshift mutations by imperfect excision.     

Hispid cotton rat ( Sigmodon hispidus ) in Nebraska: distribution, reproduction, and seasonal activity

The hispid cotton rat ( Sigmodon hispidus ) has occurred in Nebraska for about 50 years and entered the state from the south via northward movements through Kansas. However, little is known about its status or distribution in the state in recent decades. We conducted surveys for S. hispidus in southern Nebraska at historical sites and sites without previous records to determine its current status. From 2004 to 2008, we documented cotton rats at 9 of 12 historical sites in south-central and extreme southeastern parts of the state, and we captured this species at 13 new sites in southwestern and south-central Nebraska. In the past 3 decades, the distribution of S. hispidus has expanded westward but not northward in the state. An explanation for such a shift is unclear. At this northern edge of its geographical range, pregnant females were captured from early April to early October, and nonreproductive females were captured from November to January. Males with enlarged testes occurred from late March to September. Aspects of its natural history in Nebraska are similar to those reported in Kansas.