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PubMed1979

Comparisons of virulence of influenza virus recombinants in ferrets in relation to their behaviour in man and their genetic constitution.

Two parent viruses, A/Finland/4/74(H3N2) and A/Okuda/57(H2N2), virulent and attenuated respectively for man, showed similar differences of virulence in ferrets as judged by estimations of 50% minimal infectious doses (MID50), the level and persistence of nasal infection, the height and duration of pyrexia and the level of lung infection. In ferrets, two recombinant clones, WRL 94(H3N2) and WRL 105(H3N2), were almost as virulent as A/Finland and indistinguishable from one another, a result which agreed well with genetic analysis (Hay et al. 1977); the RNA pieces of these recombinants appeared identical and largely derived from the virulent parent (A/Finland). The results in ferrets did not agree with tests on clone WRL 94 in small numbers of human volunteers but they were not inconsistent with those on clone WRL 105 in larger numbers. It is possible therefore that careful tests in ferrets may yield more accurate information on the virulence of strains than limited tests in human volunteers. A rapid test for virulence in ferrets is described. It could be used to screen many additional recombinants thereby yielding information on the genetical basis of virulence and indicating possible vaccine strains for more thorough testing in ferrets and in man.

Animals↗
PubMed2006

Axes of differentiation in the bower-building cichlids of Lake Malawi.

The 500-1000 cichlid species endemic to Lake Malawi constitute one of the most rapid and extensive radiations of vertebrates known. There is a growing debate over the role natural and sexual selection have played in creating this remarkable assemblage of species. Phylogenetic analysis of the Lake Malawi species flock has been confounded by the lack of appropriate morphological characters and an exceptional rate of speciation, which has allowed ancestral molecular polymorphisms to persist within species. To overcome this problem we used amplified fragment length polymorphism (AFLP) to reconstruct the evolution of species within three genera of Lake Malawi sand-dwelling cichlids that construct elaborate male display platforms, or bowers. Sister taxa with distinct bower morphologies, and that exist in discrete leks separated by only 1-2 m of depth, are divergent in both sexually selected and ecological traits. Our phylogeny suggests that the forces of sexual and ecological selection are intertwined during the speciation of this group and that specific bower characteristics and trophic morphologies have evolved repeatedly. These results suggest that trophic morphology and bower form may be inappropriate characters for delineating taxonomic lineages. Specifically the morphological characters used to describe the genera Lethrinops and Tramitichromis do not define monophyletic clades. Using a combination of behavioural and genetic characters, we were able to identify several cryptic cichlid species on a single beach, which suggests that sand dweller species richness has been severely underestimated.

Animals↗
PubMed2006

Finding fathers: spatio-temporal analysis of paternity assignment in grey seals (Halichoerus grypus).

Molecular studies of pinniped breeding systems exhibit a broad range of agreement and disagreement with observational indices of male breeding success. Grey seal studies have reported considerable discrepancies between genetic and behavioural paternity measures that have been interpreted as evidence of previously unidentified male strategies and/or tactics. Therefore, these studies have the power to fundamentally alter our perceptions of mating systems. However, other pinniped studies exhibit no such disagreements, and one possible explanation for disparities may be sampling biases in space and time. Therefore, it is essential that potential sampling biases are examined to evaluate the likelihood of previously unidentified male strategies. We examined paternities assigned at the North Rona grey seal colony between 1999 and 2002 in relation to concurrent detailed behavioural and locational data for males and females. We found that (i) for females observed in sexual interaction(s) during their oestrus period, it was highly probable that one of the interacting males fathered their next pup; (ii) over 80% of assigned paternities agreed with observations of the in-colony behaviour and spatio-temporal proximity of the males and females involved; and (iii) a minority of females exhibit mate choice and seek sires outside their local male's home range, although evidence suggests that these females mate on the colony rather than at sea. In conclusion, nearly all paternities assigned agreed with expectation based upon detailed knowledge of the spatio-temporal patterns of individuals during the breeding season. We found little evidence of unidentified male strategies at North Rona, Scotland, whereas further examination of mechanisms of female choice may be productive.

Animals↗
PubMed1985

DNA sequence analysis of the oli1 gene reveals amino acid changes in mitochondrial ATPase subunit 9 from oligomycin-resistant mutants of Saccharomyces cerevisiae.

The nucleotide sequence of the oli1 gene encoding mitochondrial ATPase subunit 9 (76 amino acids) has been determined for five oligomycin-resistant mutants of Saccharomyces cerevisiae. Three of the mutations affect amino acids in the vicinity of the glutamic acid residue 59 at which dicylohexyl carbodiimide binds. Two other mutations lead to substitution of amino acid 23, which would lie very close to residue 59 in the folded hairpin conformation that this protein is thought to adopt in the inner mitochondrial membrane. The apposition of residues 23 and those adjacent to residue 59, lying respectively in the two hydrophobic membrane-spanning arms of subunit 9, is considered to constitute an oligomycin-binding domain. By consideration of the amino acid substitutions in those mutants cross-resistant to venturicidin, a domain of resistance for venturicidin is defined to lie within the oligomycin-binding domain, also centered on residues 23 and 59. These data also clarify the genetic recombination behaviour of alleles previously defined to form part of the oli3 locus (mutants characterized by resistance to both oligomycin and venturicidin) together with alleles defined to form part of the oli1 locus (mutants not cross-resistant to venturicidin). The oli1 and oli3 loci can now be seen to form two overlapping extended groups within the oli1 gene, with sequenced oli3 mutations being as far apart as 125 nucleotides within the subunit 9 coding region of 231 nucleotides.

Adenosine Triphosphatases↗
PubMed2001

Control of glutamate and GABA release by nociceptin/orphanin FQ in the rat lateral amygdala.

The actions of the heptadecapeptide termed nociceptin or orphanin FQ (N/OFQ) and the recently discovered putative precursor product nocistatin were examined on synaptic transmission in putative projection cells of the rat lateral amygdala using the whole-cell patch-clamp technique. N/OFQ decreased evoked non-NMDA receptor-mediated excitatory postsynaptic current (EPSC) amplitudes in a concentration-dependent manner, with a half-maximal inhibitory effect elicited by 21.8 +/- 7.5 nM and a Hill coefficient of 0.8 +/- 0.2 (n = 22). Responses were maximally suppressed to 70.3 +/- 1.7 % of the control value. The effect of N/OFQ was prevented by 1 microM [Phe1[psi](CH2-NH)Gly2]NC(1-13)NH2 (Phe[psi]N/OFQ), a substance known as an antagonist/partial agonist of the ORL receptor. GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) elicited through intra-amygdaloid stimulation were reduced to 48.0 +/- 6.8 % by 1 microM N/OFQ (n = 5). Nocistatin had no measurable effect on evoked synaptic currents or membrane properties of recorded neurons. N/OFQ reduced the frequency of spontaneous miniature EPSCs and IPSCs to 74.0 +/- 2.6 % and 84.4 +/- 1.1 %, respectively, without affecting the amplitudes. The present findings indicate that N/OFQ, but not nocistatin, inhibits the release of glutamate and GABA in the lateral amygdala, presumably by acting on presynaptic release sites. These mechanisms may add to the role of N/OFQ in reducing stress vulnerability as recently proposed on the basis of behavioural and genetic approaches.

Amygdala↗
PubMed1995

Parental exposure to hydrocarbons in Prader-Willi syndrome.

The purpose of this study was to ascertain whether parental age and parental pre-conceptional exposure to various agents differentiated children with Prader-Willi syndrome (PWS) from obese children without PWS. Two groups of patients under 25 years of age were studied, 15 persons with PWS, and 13 with PWS-like symptoms. In the PWS group deletions were detected on chromosome 15q11-q13 and parents were older. The parents' occupational and recreational exposure to environmental toxins was recorded and correlated to the clinical diagnosis, genetics and behaviour characteristics. Paternal exposure to gasoline/petrol was significantly higher in the PWS group and is suggested as a possible important factor in the aetiology of PWS.

Adolescent↗
PubMed2005

Disease progression: identification of high-risk groups and individuals for periodontitis.

AIMS: While the role of bacteria in the initiation of periodontitis is primary, a range of host-related factors influence the onset, clinical presentation and rate of progression of disease. The objectives of this review are (1) to present evidence for individual predictive factors associated with a patient's susceptibility to progression of periodontitis and (2) to describe the use of prognostic models aimed at identifying high-risk groups and individuals in a clinical setting. METHODS: Relevant publications in the English language were identified after Medline and PubMed database searches. Because of a paucity of longitudinal studies investigating factors including clinical, demographic, environmental, behavioural, psychosocial, genetic, systemic and microbiologic parameters to identify individuals at risk for disease progression, some association studies were also included in this review. FINDINGS AND CONCLUSIONS: Cigarette smoking is a strong predictor of progressive periodontitis, the effect of which is dose related. High levels of specific bacteria have been predictive of progressive periodontitis in some studies but not all. Diabetics with poor glycaemic control have an increased risk for progression of periodontitis. The evidence for the effect of a number of putative factors including interleukin-1 genotype, osteoporosis and psychosocial factors is inconclusive and requires further investigation in prospective longitudinal studies. Specific and sensitive diagnostic tests for the identification of individuals susceptible to disease progression are not yet a reality. While factors assessed independently may not be valuable in predicting risk of future attachment loss, the combination of factors in a multifactorial model may be useful in identifying individuals at risk for disease progression. A number of multifactorial models for risk assessment, at a subject level have been developed but require validation in prospective longitudinal studies.

Alcohol Drinking↗
PubMed1981

Neuroendocrine mechanisms and the aetiology of male and female homosexuality.

Theories on the classification and aetiology of male homosexuality are reviewed, particularly recent hypotheses on the role of prenatal hormonal influences on brain sexual differentiation and subsequent sexual object choice in the male. Female as well as male brain sexual differentiation may be hormonally determined, and so primary homosexuality in both sexes may be due to abnormalities in foetal exposure to hormones, leading first to physical mis-differentiation and later to homosexual behaviour in genetically and phenotypically normal men and women.

Androgens↗
PubMed1988

Analysis of a Dictyostelium chemotaxis mutant with altered chemoattractant binding.

A Dictyostelium discoideum mutant defective in folate chemotaxis has been analysed using biochemical, behavioural, and genetic methods. A subset of the cell-surface folate binding sites appeared to be locked in a high-affinity state from which folate dissociated extremely slowly. Changes in cell area and motility induced by step increases in folate required 10- to 100-fold higher concentrations than in the wild type. Folate-stimulated cyclic GMP production was also altered. Chemotactic responses to cyclic AMP as well as cyclic AMP-stimulated cyclic GMP production were normal. The mutation responsible for the chemotaxis defect, termed folA1000, was localized to linkage group IV. The alterations in folate binding and sensitivity to folate co-localized with the folA1000 mutation. We conclude that the folA1000 mutation arrests the folate chemotaxis receptor in a high affinity state that can only poorly transduce folate binding into chemotactic responses.

Chemotaxis↗
PubMed2004

Distance and force production during jumping in wild-type and mutant Drosophila melanogaster.

In many insects renowned for their jumping ability, elastic storage is used so that high forces can be developed prior to jumping. We have combined physiological, behavioural and genetic approaches to test whether elastic energy storage makes a major contribution to jumping in Drosophila. We describe a sensitive strain gauge setup, which measures the forces produced by tethered flies through their mesothoracic legs. The peak force produced by the main jumping muscle of female flies from a wild-type (Canton-S) strain is 101+/-4.4 microN [and this is indistinguishable from a second wild-type (Texas) strain]. The force takes 8.2 ms to reach its peak. The peak force is not affected significantly by altering the leg angle (femur-tibia joint angle) in the range of 75-120 degrees, but the peak force declines as the leg is extended further. Measurements of jumping ability (distance jumped) showed that female Drosophila (with their wings removed) of two wild-type strains, Canton-S and Texas, produced jumps of 28.6+/-0.7 and 30.2+/-1.0 mm (mean +/- s.e.m.). For a female wild-type Drosophila, a jump of 30 mm corresponds to a kinetic energy of 200 nJ on take-off (allowing 20% of the energy to overcome air resistance). We develop equations of motion for a linear force-time model of take-off and calculate that the time to take-off is 5.0 ms and the peak force should be 274 microN (137 microN leg(-1)). We predicted, from the role of octopamine in enhancing muscle tension in several locust muscles, that if stored elastic energy plays no part in force development, then genetic manipulation of the octopaminergic system would directly affect force production and jumping in Drosophila. Using two mutants deficient in the octopaminergic system, TbhnM18 (M18) and TyrRhono (hono), we found significantly reduced jumping distances (20.7+/-0.7 and 20.7+/-0.4 mm, respectively) and force production (52% and 55%, respectively) compared with wild type. From the reduced distance and force production in M18, a mutant deficient in octopamine synthesis, and in hono, a tyramine/octopamine receptor mutant, we conclude that in Drosophila, as in locusts, octopamine modulates escape jumping. We conclude that the fly does not need to store large quantities of elastic energy in order to make its jump because (1) the measured and calculated forces agree to within 40% and (2) the reduction in distances jumped by the mutants correlates well with their reduction in measured peak force.

Animals↗
PubMed1998

Environmentally responsive mutator systems: toward a unifying perspective.

Biology has long sought a unifying principle. The behaviour of genetically controlled mutator processes adaptively responsive to stress may reflect such a principle. Related mutators exist in diverse organisms from bacteria to mammals. Such systems have evolved from one another and have defined the very evolution of organisms. Many of these mutator systems can determine in a developmental manner a ultramutability or hypermutability throughout the genome. Though the genetic control of high levels of mutability can reflect molecular features, such mutagenic processes reflect a deeper parameter involving forces and their configurations. These configurations must generate stable or uniform configurations from unstable ones throughout the genome and organism. Directed mutation becomes a generative process attuned to non-uniform forces of local niches and to the more uniform forces of a universal niche. The manner of mutagenic, attuned response depends on the level of genomic and transgenomic organization. This is reflected in hierarchies of evolution. Directed mutation is a feature of a universal, generative ordering process, and this feature is marked by a universal dimensionless constant. It is the dynamic consequence of such directed generation which ultimately confers adaptation through dynamic completion. This suggests an underlying, unitary, and necessary dynamics connecting ultramutability systems in all organisms and would serve, in complementation with a molecular approach, to elicit new and productive research avenues. One outcome would be the illustration of a unifying principle governing biological and physical phenomena.

Adaptation, Physiological↗
PubMed1999

The complexity of the malaria vectorial system in Africa.

The malaria vectorial system in Africa is very complex. Five very efficient vector species transmit malaria: Anopheles gambiae, An. arabiensis, An. funestus, and the sometimes overlooked An. nili and An. moucheti. This paper focuses on morphological, behavioural and genetic differences observed among populations within each vector species. It emphasises that future strategies for controlling vectors should take into account this heterogeneity.

Africa↗
PubMedDate not supplied

Diabetes in Australian aboriginal and Torres Strait Islander peoples.

Type 2 diabetes arises from a complex and multifactorial set of factors, including genetic susceptibility, behaviour (including diet and exercise), early nutrition, obesity and psychosocial stress, leading to insulin resistance and pancreatic failure. These factors in turn are influenced by social and physical environmental factors. Each of these may be important determinants of the high prevalence and incidence of type 2 diabetes in Australian Aboriginal and Torres Strait Islander people. Public health interventions for primary and secondary prevention need to recognize this complexity. Although a reduction in the prevalence of obesity or diabetes in the short-medium term is rarely if ever achieved, there are documented examples of community-based programs which have been effective in reducing the risk of developing type 2 diabetes and its cardiovascular complications. Such interventions need to be community-directed and appropriate to local circumstances in order to be effective.

Australia↗
PubMed2003

['Knowledge Infrastructure for Public Health': an advisory report from the Advisory Council on Health Research].

Social, scientific and technological developments are forcing health care systems to shift the focus from disease to health and from cure to prevention. The Advisory Council on Health Research (RGO) has published an advisory report about the knowledge infrastructure serving the needs of public health in the Netherlands. The Council's concept of public health also includes aspects such as policy and health management. The Council concludes that more research is needed on the following determinants of health: environmental issues, social factors, unhealthy behaviour and genetic factors. Intervention research must focus on health protection, health promotion and disease prevention. The public health infrastructure can be improved by amalgamating research groups, establishing departments of public health at every academic medical centre, and linking service, education and research.

Health Promotion↗
PubMed2004

Current challenges in tobacco control.

Tobacco is the world's biggest preventable killer, but the circumstances of its history, the power and influence of its commerce and the nature of addiction make it a very difficult public health issue. Determinants of smoking are both individual and environmental. Genetics and environment influence to varying degrees all of the steps in a smoker's career. Persistence of use, degree of addiction to nicotine and difficulty in stopping are influenced by inherited traits and nicotine susceptibility, whereas the social environment and the individual's cognitions are the key factors in starting smoking and successfully stopping smoking. The tools available to tobacco control include influencing the social and cultural norms concerning tobacco; legislative and regulatory measures to protect the population and to limit tobacco industry marketing tactics, now encapsulated in the Framework Convention on Tobacco Control; and programmes to enhance the chance of not starting and successfully stopping. Strategies for tobacco control must work at both societal and individual levels, and directions are being taken that include genetic, pharmacological, behavioural, socio-cultural and international approaches.

Algorithms↗
PubMed1989

[Dilated cardiomyopathy--heart muscle disease of unknown origin or an autoimmune disease? New aspects of etiology, pathogenesis and clinical practice].

Recent evidence suggests that the most common form of idiopathic cardiomyopathy in our altitudes, the dilated cardiomyopathy (DCM), is a post-infectious autoimmune disease which is triggered by virus infections. In animal experiments, the development of the coxsackie virus B3 myocarditis to a congestive cardiac insufficiency resembling the clinical picture of DCM was demonstrated. In mice, species-dependent varying disease courses could be observed, which point to a genetically different behaviour of the animals' immunological reactions, either humoral or T-cell mediated immune reactions being responsible. In comparison with non-DCM patients, patients with DCM and chronic myocarditis exhibit significantly higher coxsackie virus antibody titres. Obviously, also a differently long viral persistency in the cardiac muscle plays a role, as enterovirus-specific RNA was detected in myocardial biopsies from patients with DCM. Along with myocardial fibroses, endomyocardial biopsies in DCM frequently reveal mononuclear cellular infiltrates, which, however, only in 20-25% of the cases may be regarded as chronic persisting myocarditis. The clinical and paraclinical findings in DCM and in the so-called latent cardiomyopathy are presented. In congestive heart failure, the best therapeutic results are achieved by the ACE inhibitors, along with vasodilator agents, digitalis glycosides and diuretics. Ultima ratio is the orthotopic heart transplantation, as it is only this intervention that will be able to improve the primarily bad prognosis decisively. Whether the treatment with immunosuppressive drugs exerts an influence upon the prognosis, has thus far remained an open question.

Animals↗
PubMed1986

Enzymes of catecholamine metabolism in the brains of rat strains differing in their preference for or tolerance of ethanol.

The activities of the catecholamine-synthesizing and inactivating enzymes were determined in whole brains of two pairs of rat strains differing in their genetically-determined behavioural responses to ethanol. The alcohol-tolerant (AT) rats did not show any significant differences in enzyme activities when compared with the non-tolerant (ANT) strain. The activity of tyrosine hydroxylase was found to be significantly higher in brains of the alcohol-preferring (AA) rats, than in those of the alcohol-non-preferring (ANA) strain.

Animals↗