Showing papers by "Newcastle University published in 1998"

Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation.

Abstract: The classification of diabetes mellitus and the tests used for its diagnosis were brought into order by the National Diabetes Data Group of the USA and the second World Health Organization Expert Committee on Diabetes Mellitus in 1979 and 1980. Apart from minor modifications by WHO in 1985, little has been changed since that time. There is however considerable new knowledge regarding the aetiology of different forms of diabetes as well as more information on the predictive value of different blood glucose values for the complications of diabetes. A WHO Consultation has therefore taken place in parallel with a report by an American Diabetes Association Expert Committee to re-examine diagnostic criteria and classification. The present document includes the conclusions of the former and is intended for wide distribution and discussion before final proposals are submitted to WHO for approval. The main changes proposed are as follows. The diagnostic fasting plasma (blood) glucose value has been lowered to > or =7.0 mmol l(-1) (6.1 mmol l(-1)). Impaired Glucose Tolerance (IGT) is changed to allow for the new fasting level. A new category of Impaired Fasting Glycaemia (IFG) is proposed to encompass values which are above normal but below the diagnostic cut-off for diabetes (plasma > or =6.1 to or =5.6 to <6.1 mmol l(-1)). Gestational Diabetes Mellitus (GDM) now includes gestational impaired glucose tolerance as well as the previous GDM. The classification defines both process and stage of the disease. The processes include Type 1, autoimmune and non-autoimmune, with beta-cell destruction; Type 2 with varying degrees of insulin resistance and insulin hyposecretion; Gestational Diabetes Mellitus; and Other Types where the cause is known (e.g. MODY, endocrinopathies). It is anticipated that this group will expand as causes of Type 2 become known. Stages range from normoglycaemia to insulin required for survival. It is hoped that the new classification will allow better classification of individuals and lead to fewer therapeutic misjudgements.

Language-impaired preschoolers: a follow-up into adolescence.

Abstract: This paper reports a longitudinal follow-up of 71 adolescents with a preschool history of speech-language impairment, originally studied by Bishop and Edmundson (1987). These children had been subd...

Microbial Evolution, Diversity, and Ecology: A Decade of Ribosomal RNA Analysis of Uncultivated Microorganisms

Abstract: The application of molecular biological methods to study the diversity and ecology of microorganisms in natural environments has been practiced since the mid-1980s Since that time many new insights into the composition of uncultivated microbial communities have been gained Whole groups of organisms that are only known from molecular sequences are now believed to be quantitatively significant in many environments Molecular methods have also allowed characterization of many long-recognized but poorly understood organisms These organisms have eluded laboratory cultivation and, hence, have remained enigmatic This review provides an outline of the main methods used in molecular microbial ecology, and their limitations Some discoveries, made through the application of molecular biological methods, are highlighted, with reference to morphologically distinctive, uncultivated bacteria; an important biotechnological process (wastewater treatment); and symbiotic relationships between Bacteria, Archaea and Eukarya

Building institutional capacity through collaborative approaches to urban planning

Abstract: Improving the qualities of places is attracting increasing policy and academic interest in contemporary Europe. This raises questions about the appropriate governance capacity to deliver such improvements. I argue that a key element of such capacity lies in the quality of local policy cultures. Some are well integrated, well connected, and well informed, and can mobilise readily to act to capture opportunities and enhance local conditions. Others are fragmented, lack the connections to sources of power and knowledge, and the mobilisation capacity, to organise to make a difference. In recent years, the emphasis in attempts to change urban governance capacity, particularly in Britain, has been on encouraging catalytic projects and partnerships. Recent experience across Europe suggests that wider transformative effects are difficult to achieve without careful consideration of the partnership form and how it connects to the wider policy culture. They may also have the effect of increasing the fragmentation of...

A gene related to Caenorhabditis elegans spermatogenesis factor fer-1 is mutated in limb-girdle muscular dystrophy type 2B

Abstract: The limb-girdle muscular dystrophies are a genetically heterogeneous group of inherited progressive muscle disorders that affect mainly the proximal musculature, with evidence for at least three autosomal dominant and eight autosomal recessive loci The latter mostly involve mutations in genes encoding components of the dystrophin-associated complex; another form is caused by mutations in the gene for the muscle-specific protease calpain 3 Using a positional cloning approach, we have identified the gene for a form of limb-girdle muscular dystrophy that we previously mapped to chromosome 2p13 (LGMD2B) This gene shows no homology to any known mammalian gene, but its predicted product is related to the C elegans spermatogenesis factor fer-1 We have identified two homozygous frameshift mutations in this gene, resulting in muscular dystrophy of either proximal or distal onset in nine families The proposed name 'dysferlin' combines the role of the gene in producing muscular dystrophy with its C elegans homology

A study of performance on tests from the CANTAB battery sensitive to frontal lobe dysfunction in a large sample of normal volunteers: Implications for theories of executive functioning and cognitive aging

Abstract: Several tests from the CANTAB neuropsychological test battery previously shown to be sensitive to frontal lobe dysfunction were administered to a large group of normal volunteers (N = 341) ranging in age from 21 to 79 years The main tests included a computerized form of the Tower of London test of planning, a self-ordered spatial working memory task, and a test of attentional set formation and shifting A computerized form of the Corsi spatial span task was also given Age-related graded declines in performance were seen, sometimes in a discontinuous manner, especially for the attentional set shifting task (at the extradimensional shift stage) Patterns of deficits reminiscent of frontal lobe or basal ganglia damage were observed in the oldest age group (74–79) However, overall the data were only partially consistent with the hypothesis that frontal lobe functions are the most sensitive to effects of aging Factor analyses showed that performance in the executive tests was not simply related to a measure of fluid intelligence, and their performance had a factor loading structure distinct from that for the CANTAB tests of visual memory and learning previously administered to the same sample Finally, only limited support was found for the hypothesis that cognitive aging depends on slowed information processing (JINS, 1998, 4, 474–490)

Competitive altruism: from reciprocity to the handicap principle

Abstract: Current work on cooperation is focused on the theory of reciprocal altruism. However, reciprocity is just one way of getting a return on an investment in altruism and is difficult to apply to many examples. Reciprocity theory addresses how animals respond dynamically to others so as to cooperate without being exploited. I discuss how introducing differences in individual generosity together with partner choice into models of reciprocity can lead to an escalation in altruistic behaviour. Individuals may compete for the most altruistic partners and non-altruists may become ostracized. I refer to this phenomenon as competitive altruism and propose that it can represent a move away from the dynamic responsiveness of reciprocity. Altruism may be rewarded in kind, but rewards may be indirectly accrued or may not involve the return of altruism at all, for example if altruists tend to be chosen as mates. This variety makes the idea of competitive altruism relevant to behaviours which cannot be explained by reciprocity. I consider whether altruism might act as a signal of quality, as proposed by the handicap principle. I suggest that altruistic acts could make particularly effective signals because of the inherent benefits to receivers. I consider how reciprocity and competitive altruism are related and how they may be distinguished.

M-Cell Surface β1 Integrin Expression and Invasin-Mediated Targeting of Yersinia pseudotuberculosis to Mouse Peyer’s Patch M Cells

Abstract: Quantitative analysis of Yersinia pseudotuberculosis infection of murine gut loops revealed that significantly more wild-type bacteria associated with Peyer’s patch M cells than with dome enterocytes or goblet cells. An invasin-deficient mutant was significantly attenuated for M-cell invasion, while β1 integrin expression was demonstrated in the apical membranes of M cells but not enterocytes. M-cell targeting by Yersinia pseudotuberculosis in vivo may, therefore, be mediated primarily by the interaction of invasin with cell surface β1 integrins.

Analysis of temporal structure in sound by the human brain.

Abstract: For over a century, models of pitch perception have been based on the frequency composition of the sound. Pitch phenomena can also be explained, however, in terms of the time structure, or temporal regularity, of sounds. To locate the mechanism for the detection of temporal regularity in humans, we used functional imaging and a 'delay-and-add' noise, which activates all frequency regions uniformly, like noise, but which nevertheless produces strong pitch perceptions and tuneful melodies. This stimulus has temporal regularity that can be systematically altered. We found that the activity of primary auditory cortex increased with the regularity of the sound. Moreover, a melody composed of delay-and-add 'notes' produced a distinct pattern of activation in two areas of the temporal lobe distinct from primary auditory cortex. These results suggest a hierarchical analysis of time structure in the human brain.

White, European, Western, Caucasian, or what? Inappropriate labeling in research on race, ethnicity, and health.

Abstract: The request for scientifically appropriate terminology in research on race, ethnicity, and health has largely bypassed the term White. This and other words, such as Caucasian, are embedded in clinical and epidemiological discourse, yet they are rarely defined. This commentary analyzes the issue from the perspective of the epidemiology of the health of minority ethnic and racial groups in Europe and the United States. Minority groups are usually compared with populations described as White, Caucasian, European, Europid, Western, Occidental, indigenous, native, and majority. Such populations are heterogeneous, the labels nonspecific, and the comparisons misleading. Terminology that reflects the research purpose-for examples, reference, control, or comparison--is better (unlike White, these terms imply no norm, allowing neither writers nor readers to make stereotyped assumptions about the comparison populations. This paper widens the debate on nomenclature for racial and ethnic groups. Many issues need explo...

Differential targeting of MAP kinases to the ETS‐domain transcription factor Elk‐1

Abstract: The activation of MAP kinase (MAPK) signal transduction pathways results in the phosphorylation of transcription factors by the terminal kinases in these cascades. Different pathways are activated by mitogenic and stress stimuli, which lead to the activation of distinct groups of target proteins. The ETS-domain transcription factor Elk-1 is a substrate for three distinct classes of MAPKs. Elk-1 contains a targeting domain, the D-domain, which is distinct from the phosphoacceptor motifs and is required for efficient phosphorylation and activation by the ERK MAPKs. In this study, we demonstrate that members of the JNK subfamily of MAPKs are also targeted to Elk-1 by this domain. Targeting via this domain is essential for the efficient and rapid phosphorylation and activation of Elk-1 both in vitro and in vivo. The ERK and JNK MAPKs use overlapping yet distinct determinants in the D-domain for targeting to Elk-1. In contrast, members of the p38 subfamily of MAPKs are not targeted to Elk-1 via this domain. Our data therefore demonstrate that different classes of MAPKs exhibit differential requirements for targeting to Elk-1.

Adsorption of gases on a carbon molecular sieve used for air separation: Linear adsorptives as probes for kinetic selectivity

Abstract: The adsorption of oxygen, nitrogen, and a series of gases/vapors with linear structures (carbon monoxide, carbon dioxide, nitrous oxide, acetylene and carbon disulfide) on a carbon molecular sieve typical of the materials used for air separation were studied over a range of temperatures as a function of pressure in order to understand further the mechanism of air separation. The ratios of the rate constants (kO2/kN2) were typically 25 for the carbon molecular sieve used thereby demonstrating the molecular sieving characteristics. The adsorption kinetics obey a linear driving force (LDF) mass transfer model for most of the gases and experimental conditions studied. However there were deviations from the LDF model for carbon dioxide and nitrous oxide. In the case of the former, the kinetic models ranged from LDF through a combined barrier resistance/diffusion model to Fickian diffusion depending on the experimental conditions. The adsorption rate constants increase exponentially with increasing surface cove...

Role of mitochondrial DNA mutations in human aging: implications for the central nervous system and muscle.

Abstract: It has been proposed that one mechanism for nerve and muscle dysfunction with age involves the mitochondria. Mitochondria contain the only DNA outside the nucleus in mammalian cells. Mitochondrial DNA (mtDNA) has a high mutation rate, and low levels of pathogenic mutations have been found in tissues from elderly subjects. However, the role of these mutations in the aging process is uncertain unless a mechanism can be identified that would lead to a biochemical defect. In muscle tissue from normal elderly subjects we show that there are muscle fibers with very low activity of cytochrome c oxidase, suggestive of a mtDNA defect. In these cytochrome c oxidase-deficient fibers we have found very high levels of mutant mtDNA. In addition, different mtDNA mutations are present in different fibers, which explains why there is a low overall incidence of an individual mutation in tissues from elderly subjects. These studies show a direct age-related correlation between a biochemical and genetic defect in normal human tissues and that mtDNA abnormalities are involved in the aging process in human muscle.

Pseudomonas cellulose-binding domains mediate their effects by increasing enzyme substrate proximity

Abstract: To investigate the mode of action of cellulose-binding domains (CBDs), the Type II CBD from Pseudomonas fluorescens subsp. cellulosa xylanase A (XYLACBD) and cellulase E (CELECBD) were expressed as individual entities or fused to the catalytic domain of a Clostridium thermocellum endoglucanase (EGE). The two CBDs exhibited similar Ka values for bacterial microcrystalline cellulose (CELECBD, 1.62x10(6) M-1; XYLACBD, 1.83x10(6) M-1) and acid-swollen cellulose (CELECBD, 1.66x10(6) M-1; XYLACBD, 1.73x10(6) M-1). NMR spectra of XYLACBD titrated with cello-oligosaccharides showed that the environment of three tryptophan residues was affected when the CBD bound cellohexaose, cellopentaose or cellotetraose. The Ka values of the XYLACBD for C6, C5 and C4 cello-oligosaccharides were estimated to be 3.3x10(2), 1.4x10(2) and 4.0x10(1) M-1 respectively, suggesting that the CBD can accommodate at least six glucose molecules and has a much higher affinity for insoluble cellulose than soluble oligosaccharides. Fusion of either the CELECBD or XYLACBD to the catalytic domain of EGE potentiated the activity of the enzyme against insoluble forms of cellulose but not against carboxymethylcellulose. The increase in cellulase activity was not observed when the CBDs were incubated with the catalytic domain of either EGE or XYLA, with insoluble cellulose and a cellulose/hemicellulose complex respectively as the substrates. Pseudomonas CBDs did not induce the extension of isolated plant cell walls nor weaken cellulose paper strips in the same way as a class of plant cell wall proteins called expansins. The XYLACBD and CELECBD did not release small particles from the surface of cotton. The significance of these results in relation to the mode of action of Type II CBDs is discussed.

A homeobox gene, HLXB9, is the major locus for dominantly inherited sacral agenesis

Abstract: Partial absence of the sacrum is a rare congenital defect which also occurs as an autosomal dominant trait; association with anterior meningocoele, presacral teratoma and anorectal abnormalities constitutes the Currarino triad (MIM 176450). Malformation at the caudal end of the developing notochord at approximately Carnegie stage 7 (16 post-ovulatory days), which results in aberrant secondary neurulation, can explain the observed pattern of anomalies. We previously reported linkage to 7q36 markers in two dominantly inherited sacral agenesis families. We now present data refining the initial subchromosomal localization in several additional hereditary sacral agenesis (HSA) families. We excluded several candidate genes before identifying patient-specific mutations in a homeobox gene, HLXB9, which was previously reported to map to 1q41-q42.1 and to be expressed in lymphoid and pancreatic tissues.

Deep acceptors trapped at threading-edge dislocations in gan

Abstract: Local-density-functional methods are used to examine the behavior of the oxygen defect, gallium vacancy, and related defect complexes trapped at threading-edge dislocations in GaN. These defects are found to be particularly stable at the core of the dislocation where oxygen sits twofold coordinated in a bridge position. VGa-ON is found to be a deep double acceptor, VGa-(O,N)2 is a deep single acceptor, and VGa-(ON)3 at the dislocation core is electrically inactive. We suggest that the first two defects are responsible for a deep acceptor level associated with the midgap yellow luminescence band. © 1998 The American Physical Society.

Right parietal cortex is involved in the perception of sound movement in humans.

Abstract: Changes in the delay (phase) and amplitude of sound at the ears are cues for the analysis of sound movement. The detection of these cues depends on the convergence of the inputs to each ear, a process that first occurs in the brainstem. The conscious perception of these cues is likely to involve higher centers. Using novel stimuli that produce different perceptions of movement in the presence of identical phase and amplitude modulation components, we have demonstrated human brain areas that are active specifically during the perception of sound movement. Both functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) demonstrated the involvement of the right parietal cortex in sound movement perception with these stimuli.

The Elk-1 ETS-domain transcription factor contains a mitogen-activated protein kinase targeting motif.

Abstract: The phosphorylation of transcription factors by mitogen-activated protein kinases (MAP) is a pivotal event in the cellular response to the activation of MAP kinase signal transduction pathways. Mitogenic and stress stimuli activate different pathways and lead to the activation of distinct groups of target proteins. Elk-1 is targeted by three distinct MAP kinase pathways. In this study, we demonstrate that the MAP kinase ERK2 is targeted to Elk-1 by a domain which is distinct from, and located N-terminally to, its phosphoacceptor motifs. Targeting via this domain is essential for the efficient and rapid phosphorylation of Elk-1 in vitro and full and rapid activation in vivo. Specific residues involved in ERK targeting have been identified. Our data indicate that the targeting of different classes of MAP kinases to their nuclear substrates may be a common mechanism to increase the specificity and efficiency of this signal transduction pathway.

Development of cooperative relationships through increasing investment

Abstract: Reciprocal altruism1 can become established among selfish, unrelated individuals if they use responsive strategies such as ‘tit-for-tat’2,3,4. This result raises the fundamental question: how altruistic should one be? The problem is difficult to solve using current ‘prisoner's dilemma’ based models because they allow only the discrete choice of cooperating or defecting. In reality, however, cooperation is rarely all-or-nothing. Furthermore, if cooperative investment is variable, a new and more subtle kind of cheating becomes possible: individuals may invest slightly less than their partner. A concern is that this ‘short-changing’ will erode cooperative ventures. Here we show that cooperation can thrive despite variable investment through the new strategy of ‘raise-the-stakes’. This strategy offers a small amount on first meeting and then, if matched, raises its investment, something that no strategy in the discrete model can do. We show that such behaviour can readily invade a population of non-altruists and cannot be effectively exploited. The practice of ‘testing the water’ rather than making sudden cooperative ‘leaps of faith’ powerfully reinforces the stability and effectiveness of reciprocity.

Deriving Petri nets from finite transition systems

Abstract: This paper presents a novel method to derive a Petri net from any specification model that can be mapped into a state-based representation with arcs labeled with symbols from an alphabet of events (a Transition System, TS). The method is based on the theory of regions for Elementary Transition Systems (ETS). Previous work has shown that, for any ETS, there exists a Petri Net with minimum transition count (one transition for each label) with a reachability graph isomorphic to the original Transition System. Our method extends and implements that theory by using the following three mechanisms that provide a framework for synthesis of safe Petri nets from arbitrary TSs. First, the requirement of isomorphism is relaxed to bisimulation of TSs, thus extending the class of synthesizable TSs to a new class called Excitation-Closed Transition Systems (ECTS). Second, for the first time, we propose a method of PN synthesis for an arbitrary TS based on mapping a TS event into a set of transition labels in a PN. Third, the notion of irredundant region set is exploited, to minimize the number of places in the net without affecting its behavior. The synthesis method can derive different classes of place-irredundant Petri Nets (e.g., pure, free choice, unique choice) from the same TS, depending on the constraints imposed on the synthesis algorithm. This method has been implemented and applied in different frameworks. The results obtained from the experiments have demonstrated the wide applicability of the method.