A 'dynamic' landscape of fear: prey responses to spatiotemporal variations in predation risk across the lunar cycle.

Ambiguous empirical support for 'landscapes of fear' in natural systems may stem from failure to consider dynamic temporal changes in predation risk. The lunar cycle dramatically alters night-time visibility, with low luminosity increasing hunting success of African lions. We used camera-trap data from Serengeti National Park to examine nocturnal anti-predator behaviours of four herbivore species. Interactions between predictable fluctuations in night-time luminosity and the underlying risk-resource landscape shaped herbivore distribution, herding propensity and the incidence of 'relaxed' behaviours. Buffalo responded least to temporal risk cues and minimised risk primarily through spatial redistribution. Gazelle and zebra made decisions based on current light levels and lunar phase, and wildebeest responded to lunar phase alone. These three species avoided areas where likelihood of encountering lions was high and changed their behaviours in risky areas to minimise predation threat. These patterns support the hypothesis that fear landscapes vary heterogeneously in both space and time.

Rescue of neurophysiological phenotype seen in PrP null mice by transgene encoding human prion protein.

The prion protein (PrP) is central to the aetiology of the prion diseases, transmissible neurodegenerative conditions of humans and animals. PrP null mice show abnormalities of synaptic neurophysiology, in particular weakened GABAA receptor-mediated fast inhibition and impaired long-term potentiation in the hippocampus. Here we demonstrate that this PrP null phenotype is rescued in mice with a high copy number of a transgene encoding human PrP but not in low copy number mice, confirming the specificity of the phenotype for loss of function of PrP. The ability of human PrP to compensate for loss of murine PrP will allow direct study of the functional consequences of the 18 human PrP mutations, which cause the inherited prion diseases; this phenotype can now form the basis of the first functional assay for PrP.

Identifying the social context of single- and mixed-species group formation in large African herbivores.

Despite continued interest in mixed-species groups, we still lack a unified understanding of how ecological and social processes work across scales to influence group formation. Recent work has revealed ecological correlates of mixed-species group formation, but the mechanisms by which concomitant social dynamics produce these patterns, if at all, is unknown. Here, we use camera trap data for six mammalian grazer species in Serengeti National Park. Building on previous work, we found that ecological variables, and especially forage quality, influenced the chances of species overlap over small spatio-temporal scales (i.e. on the scales of several metres and hours). Migratory species (gazelle, wildebeest and zebra) were more likely to have heterospecific partners available in sites with higher forage quality, but the opposite was true for resident species (buffalo, hartebeest and topi). These findings illuminate the circumstances under which mixed-species group formation is even possible. Next, we found that greater heterospecific availability was associated with an increased probability of mixed-species group formation in gazelle, hartebeest, wildebeest and zebra, but ecological variables did not further shape these patterns. Overall, our results are consistent with a model whereby ecological and social drivers of group formation are species-specific and operate on different spatio-temporal scales. This article is part of the theme issue 'Mixed-species groups and aggregations: shaping ecological and behavioural patterns and processes'.

Prion diseases.

There have been remarkably rapid advances in the understanding of prion diseases over the past year. The controversial notion that the transmissible agent may be an abnormal isoform of a host-encoded protein, the prion protein, is now gaining wide acceptance. The conundrum of how a disease can both be inherited as an autosomal dominant condition and also be experimentally transmissible by inoculation is beginning to make sense.

Conformational properties of the prion octa-repeat and hydrophobic sequences.

We have used circular dichroism to study synthetic peptides from two important regions of the prion protein: the N-terminal octa-repeat domain and a highly conserved hydrophobic section. Our results show that the octa-repeat sequence in free solution can adopt a non-random, extended conformation with properties similar to the poly-L-proline type II left-handed helix. We also show that the conformation can be changed by temperature, organic solvents (e.g. acetonitrile) and on binding to phospholipid vesicles. We compared CD data from two peptides corresponding to the hydrophobic region between residues 106 and 136 which contained either methionine or valine at position 129. This variation represents a common polymorphism in humans which has been shown to influence predisposition towards iatrogenic and sporadic CJD. There was no detectable difference between the CD spectra of these peptides irrespective of the solvent conditions we used.

A prion disease with a novel 96-base pair insertional mutation in the prion protein gene.

There are coding mutations in the prion protein gene in familial Creutzfeldt-Jakob disease (CJD), Gerstmann-Straussler-Scheinker disease, and other phenotypes that make up the inherited prion diseases. Insertional mutations consisting of two, five, six, seven, eight, and nine additional octapeptide repeat elements are seen in the inherited prion diseases and usually present as atypical dementias with considerable intrafamilial phenotypic variability. A four-octarepeat insertion was reported previously in an individual without neurodegenerative disease who died of hepatic cirrhosis. Here we report a novel four-octarepeat insertional mutation in a case with classical clinical, electroencephalographic and histopathologic features of CJD with the unusual finding of pronounced prion protein immunoreactivity of the molecular layer of the cerebellum.

Sex determining genes.

The development of a male or female phenotype is dependent upon the expression of sets of sex specific differentiation genes early in embryonic life. Selecting the appropriate set of genes requires a primary signal that is unique to males or females, and a set of sex determining genes that respond to the primary signal leading to activation of the correct differentiation pathway. A general model for sex determination is emerging from a study of developmental genes in a number of species. This article describes a number of sex determining genes and genetic pathways in detail, and discusses how apparently dissimilar pathways may have derived from each other during evolution.

Monoclonal antibodies against the complement control protein factor H (beta 1 H).

Two mouse monoclonal antibodies against the human complement control protein, Factor H (beta 1H), are described. The antibodies are both IgG - gamma 1 - subclass and are directed against different epitopes on the human Factor H molecule. One of the antibodies, MRC OX 24, increases the cofactor activity of Factor H in Factor I-mediated cleavage of soluble C3b. The second antibody, MRC OX 23, which has no effect alone, reduces the increase in cofactor activity observed in the presence of the first antibody. However, MRC OX 24 inhibits the binding of 125I-labelled Factor H to surface-bound C3b (EAC3b). Again MRC OX 23 alone does not have an effect but decreases the inhibition in 125I-labelled Factor H binding to EAC3b observed with MRC OX 24. These studies show clearly that the interaction of Factor H with soluble C3b is different to its interaction with surface-bound C3b. In an indirect immunoprecipitation system using these monoclonal antibodies, single-chain molecules of 150 000 mol.wt. are specifically precipitated from human serum and also from the sera of other primates - rhesus monkey, cynomolgus monkey, and African green monkey. There was no precipitation from sera of cow, pig, sheep, chick, or rabbit. Using a radioimmunoassay with radiolabelled monoclonal MRC OX 23, the concentration of Factor H in human plasma was determined.

Inherited prion disease (PrP lysine 200) in Britain: two case reports.

OBJECTIVE: To identify cases of inherited prion diseases in Britain and to assess their phenotypic features. DESIGN: Screening study of patients suspected clinically to have Creutzfeldt-Jakob disease and other neurodegenerative diseases by prion protein gene analysis. SETTING: Biochemical research department. SUBJECTS: Patients suspected to have Creutzfeldt-Jakob disease and other neurodegenerative diseases. RESULTS: Two patients with symptoms characteristic of sporadic Creutzfeldt-Jakob disease were found to have inherited prion protein disease (PrP lysine 200), with a mutation at codon 200 of the prion protein gene. Both were homozygous at codon 129 of the gene. One patient was a man aged 58 of British descent while the other was of Libyan Jewish origin. CONCLUSION: Two foci of inherited prion disease are known, among Libyan Jews and in Slovakia. A separate British focus of the disease may also exist. Heterozygosity at codon 129 may lead to reduced penetrance of the mutation.

Human prion diseases.

The past year has seen considerable advances in our understanding of the prion diseases, and there is increasing acceptance that the transmissible agent in these diseases may be an abnormal isoform of a normal host encoded protein. Molecular genetic studies have led to a new appreciation of the phenotypic spectrum of the prion diseases as the inherited forms of these conditions can now be diagnosed by a direct gene test. The conundrum of how a disease can be both inherited and transmissible is beginning to make sense.

Molecular genetics of human prion diseases.

Human prion diseases occur in inherited, sporadic and acquired forms. The inherited forms are associated with coding mutations in the prion protein gene and the identification of one of these pathogenic mutations allows definitive diagnosis and has resulted in a widening of the previously recognized phenotypic spectrum of these diseases. Study of acquired prion disease provides evidence for genetic susceptibility to development of disease following treatment with contaminated pituitary hormones. Sporadic prion disease occurs predominantly in individuals homozygous with respect to a common PrP polymorphism at residue 129. The identification of pathogenic PrP alleles and the role of the codon 129 PrP gene polymorphism in determining susceptibility to prion disease provides strong support for the idea that an abnormal isoform of PrP, PrPSc, is the principal constituent of the prion and that its propagation involves direct PrP-PrP interactions which occur most readily between identical PrP molecules.

Mutations and polymorphisms in the prion protein gene.

Inherited forms of prion diseases are associated with mutations in the prion protein gene. A common polymorphism at codon 129 is also implicated in the predisposition of individuals to sporadic or iatrogenic forms of the disease. This update lists all the currently published mutations and polymorphisms together with their clinical phenotypes, and discusses the significance of the codon 129 genotype in inherited, sporadic, and iatrogenic cases. There are two categories of mutation. Insertions of additional numbers of an octapeptide lying within an octapeptide repeat region now account for six variations and there are also six point mutations. The identification of mutations in this gene has lead to a broadening of the spectrum of clinical phenotypes that can be classified as prion diseases and have provided an important tool in the diagnosis of familial dementias.

Prion diseases in humans and their relevance to other neurodegenerative diseases.

Molecular genetics has led to considerable advances in our understanding of the transmissible spongiform encephalopathies. The identification of pathogenic mutations in the prion protein gene has enabled a molecular reclassification of the familial forms of these diseases, which may now be referred to as inherited prion diseases. Prion diseases of both humans and animals are associated with deposition of an abnormal isoform of a host-encoded protein, the prion protein (PrP). Human prion diseases have inherited, sporadic and acquired forms. A considerable body of evidence now supports the idea that the transmissible agent in these diseases may be an abnormal isoform of the prion protein. The identification of pathogenic mutations in the PrP gene has enabled the identification of cases of inherited prion disease that would not have been recognised using existing clinical and pathological diagnostic criteria. Since marked clinical and neuropathological overlap between the different neurodegenerative disorders is well recognised, PrP gene analysis is of increasing importance in differential diagnosis. Frontal lobe dementia of non-Alzheimer type and Pick's disease share a number of important clinical and pathological features with prion diseases, and could be considered as candidate prion diseases. However, we have not been able to demonstrate either PrP mutations or the presence of the disease-associated isoform of prion protein in several well-characterised families with these disorders.

Human trophoblast and the choriocarcinoma cell line BeWo express a truncated HLA Class I molecule.

Extravillous trophoblast from normal human placenta has been shown previously to express an unusual form of HLA class I molecule, as does a choriocarcinoma cell line, BeWo. This molecule has a H chain of approximately 40 kDa and appears to be nonpolymorphic. We have isolated and sequenced a HLA class I cDNA clone, which probably corresponds to this molecule, from a library derived from BeWo. The nucleotide sequence shows a high degree of homology with the published sequence of a genomic clone, HLA 6.0, which is the product of a class I locus other than A, B, or C, (provisionally designated "HLA G"). The expressed product of this locus has not previously been localized. We have used the polymerase chain reaction to demonstrate the presence of similar HLA class I sequences in cDNA from normal extravillous trophoblast. Although there is some nucleotide sequence polymorphism the amino acid sequence of this molecule is conserved. It is therefore unlikely to provoke immune responses even though it is found at the fetal-maternal interface.

Genetic predisposition to iatrogenic Creutzfeldt-Jakob disease.

The spongiform encephalopathy Creutzfeldt-Jakob disease (CJD) has been transmitted to man via administration of growth hormone and gonadotropin extracted from large pooled batches of human cadaveric pituitary glands. In the UK, 1908 individuals were exposed to potentially contaminated growth hormone, of whom 6 have so far manifested CJD. Examination of the prion protein genes of all these cases and of a single case of gonadotropin-related CJD showed that 4 had the uncommon valine 129 homozygous genotype indicating genetic susceptibility to prion infection. Such genetic susceptibility may be important in the aetiology of sporadic CJD disease.