The helminth parasite community of European badgers (Meles meles) in Ireland.

The European badger (Meles meles) is Ireland's largest terrestrial carnivore. Since first being identified as a wildlife reservoir of bovine tuberculosis in 1974 there has been an increased research focus into the behaviour of these ecologically important mammals in the Republic of Ireland (ROI). However, to date there has never been an assessment of the helminth parasite community of Irish badgers. This study of 289 badgers found helminth infection to be endemic within the sample population and we report for the first time the prevalence, abundance, intensity and aggregation of helminth infection in ROI. Eight distinct helminth taxa were recorded: Aelurostrongylus falciformis, Crenosoma melesi, Eucoleus aerophilus, Species A, Strongyloides spp., Uncinaria criniformis, and two unidentifiable but morphologically distinct nematodes. All helminths belong to the taxon Nematoda, and this is the first report of an exclusively nematode community across the badger's Eurasian distribution. Infection was not significantly influenced by the host sex, region of origin or season of sampling.

Towards a blood-stage vaccine for malaria: are we following all the leads?

Although the malaria parasite was discovered more than 120 years ago, it is only during the past 20 years, following the cloning of malaria genes, that we have been able to think rationally about vaccine design and development. Effective vaccines for malaria could interrupt the life cycle of the parasite at different stages in the human host or in the mosquito. The purpose of this review is to outline the challenges we face in developing a vaccine that will limit growth of the parasite during the stage within red blood cells--the stage responsible for all the symptoms and pathology of malaria. More than 15 vaccine trials have either been completed or are in progress, and many more are planned. Success in current trials could lead to a vaccine capable of saving more than 2 million lives per year.

Transgenic expression of the FTDP-17 tauV337M mutation in brain dissociates components of executive function in mice.

Frontotemporal lobe dementia (FTD) is a heterogeneous range of disorders, a subset of which arise from fully penetrant, autosomal dominant point mutations in the gene coding for the microtubule associated protein tau. These genetic tauopathies are associated with complex behavioural/cognitive disturbances, including compromised executive function. In the present study, we modelled the effects of the FTD with Parkinsonism linked to chromosome 17 (FTDP-17) tauV337M mutation (known as the Seattle Family A mutation) expressed in mice on executive processes using a novel murine analogue of the Stroop task. Employing biconditional discrimination procedures, Experiment 1 showed that normal mice, but not mice with excitotoxic lesions of the medial prefrontal cortex, were able to use context cues to resolve response conflict generated by incongruent stimulus compounds. In contrast to predictions, response conflict resolution was not disrupted by the tauV337M mutation (Experiment 2). However, while context appropriate actions were goal-directed in wild-type mice, performance of tauV337M mice was not goal-directed (Experiment 3). The results indicate that the tauV337M mutation in mice disrupts, selectively, a subset of processes related to executive function.

Quality control in the national bovine tuberculosis eradication programme in Ireland.

The Irish bovine tuberculosis (BTB) eradication programme operates under national legislation and fulfils the requirements of the European Union Trade Directive 64/432. The programme includes annual single intradermal comparative tuberculin test (SICTT) screening of all herds, prompt removal of test reactors and further consequential retesting of herds. Continuous evaluation of all relevant activities is essential to deliver an effective national programme and to reassure all stakeholders thatthe highest possible standards are attained. Quality control (QC) is a recognised process in the delivery of quality products or services. This paper presents a review of QC in the BTB eradication programme in Ireland, with particular emphasis on field surveillance and the assessment of private veterinary practitioner performance. A broad range of programme elements subjected to QC are described, including personnel, training, equipment, tuberculins and laboratories.

Sensory characteristics and consumer preference for meat from guinea fowl fed hevea seed meal or cashew nut meal supplemented diets.

This study is part of a series of studies on the possibility of substituting alternative protein source supplements to the diet of guinea fowl in order to improve food security in the fight against poverty on the African Continent. This study assesses the identified sensory characteristics of guinea fowl meat and consumer preferences to determine if the possible alternative supplements identified result in a product acceptable to consumers and if consumer preference was evident. Indigenous guinea fowl or selected breed (Galor animals) were fed a control diet C, a commercial diet I (diet used for guinea fowl in Côte d'Ivoire), or one of 2 experimental diets N (diet C supplemented with 15% cashew nut meal) or diet H (diet C supplemented with 15% detoxified hevea seed meal). Meat samples were assessed by 120-trained people using 18 sensory attributes. Principal component analysis (PCA) showed that meats from guinea fowl fed diet C or diet I were clearly distinguished from guinea fowl fed N or H diets and that meat of indigenous guinea fowl or Galor animals were also clearly distinguished. The results of the hierarchical group analysis showed that meat from guinea fowl fed diet H was the preferred guinea fowl meat. A first partial least squares regression PLSR1 identified the relationships between guinea fowl meat samples, their sensory attributes and consumer preference and showed that 82.6% of the sensory data of the first 2 principal components accounted for 95.5% of the preference. The PLSR2 identified the relationships between guinea fowl samples, their sensory attributes, and their biochemical characteristics and showed that the fat content of the meat determined the intensity of flavor, odor, juiciness, and tenderness of the meat. Our results showed that meat from birds fed diet H was preferred, and thus emphasized the existence of a place for the use of hevea seed meal in guinea fowl diet in Côte d'Ivoire.

Vaccine-induced cytotoxic T lymphocytes protect against retroviral challenge.

The development of prophylactic vaccines against retroviral diseases has been impeded by the lack of obvious immune correlates for protection. Cytotoxic T-lymphocyte (CTL), CD4-lymphocyteS, chemokine and/or antibody responses have all been associated with protection against HIV and AIDS; however, effective and safe vaccination strategies remain elusive. Here we show that vaccination with a minimal ovine CTL peptide epitope identified within gp51 of the retrovirus bovine leukemia virus (BLV), consistently induced peptide-specific CTLs. Only sheep whose CTLs were also capable of recognizing retrovirus-infected cells were fully protected when challenged with BLV. This retrovirus displays limited sequence variation; thus, in the relative absence of confounding CTL escape variants, virus-specific CTLs targeting a single epitope were able to prevent the establishment of a latent retroviral infection.

New multi-determinant strategy for a group A streptococcal vaccine designed for the Australian Aboriginal population.

Infection with group A streptococci can result in acute and post-infectious pathology, including rheumatic fever and rheumatic heart disease. These diseases are associated with poverty and are increasing in incidence, particularly in developing countries and amongst indigenous populations, such as Australia's Aboriginal population, who suffer the highest incidence worldwide. Immunity to group A streptococci is mediated by antibodies against the M protein, a coiled-coil alpha helical surface protein of the bacterium. Vaccine development faces two substantial obstacles. Although opsonic antibodies directed against the N terminus of the protein are mostly responsible for serotypic immunity, more than 100 serotypes exist. Furthermore, whereas the pathogenesis of rheumatic fever is not well understood, increasing evidence indicates an autoimmune process. To develop a suitable vaccine candidate, we first identified a minimum, helical, non-host-cross-reactive peptide from the conserved C-terminal half of the protein and displayed this within a non-M-protein peptide sequence designed to maintain helical folding and antigenicity, J14 (refs. 8,9). As this region of the M protein is identical in only 70% of group A streptococci isolates, the optimal candidate might consist of the conserved determinant with common N-terminal sequences found in communities with endemic group A streptococci. We linked seven serotypic peptides with J14 using a new chemistry technique that enables the immunogen to display all the individual peptides pendant from an alkane backbone. This construct demonstrated excellent immunogenicity and protection in mice.

Restricted or absent immune responses in human populations to Plasmodium falciparum gamete antigens that are targets of malaria transmission-blocking antibodies.

We have studied the antibodies to sexual stage antigens of Plasmodium falciparum in human sera from Papua New Guinea where intense transmission of P. falciparum occurs as well as the less prevalent P. malariae and P. vivax. In extracts of gametes of P. falciparum we have studied the reactivity of serum antibodies with antigens labeled with 125I on the surface of the gametes as well as intracellular gamete antigens. A prominent 27-kD sexual stage-specific intracellular protein was recognized more or less in proportion to the general antibody response to gamete proteins. The response to the gamete surface proteins, however, was quite unrepresentative of the general antibody response to the intracellular gamete proteins. No antibodies were detected against Pfs25, a 21-kD protein expressed on zygotes and ookinetes of P. falciparum and known to be a sensitive target of malaria transmission-blocking antibodies. The antibody response to two other target antigens of transmission-blocking antibodies on the surface of gametes of P. falciparum, a 230- and a 48- and 45-kD protein doublet, was very variable and independent of the response to the internal protein antigens. Several possibilities are discussed that may account for the variable response to these gamete surface antigens in individuals with otherwise good antibody responses to internal sexual stage proteins. Among these is the possibility that there is MHC restriction of the immune response to the gamete surface antigens in the human population. This interpretation accords well with evidence for MHC-restricted immune response to the same P. falciparum gamete surface antigens in studies with H-2 congenic mice (24).

Genetic control of the immune response in mice to a Plasmodium falciparum sporozoite vaccine. Widespread nonresponsiveness to single malaria T epitope in highly repetitive vaccine.

Different H-2 congenic strains of mice were immunized with a P. falciparum sporozoite vaccine currently being tested in humans, or with different segments of the vaccine molecule. Specific IgG production or lymph node cell proliferation in response to different antigens was then determined. Only four of seven strains (representing three of eight possible different class II restriction molecules) responded to the vaccine. Of those restriction molecules, only one, I-Ab, was associated with a response to a malaria-encoded T epitope [contained within NP(NANP)3NA], while the other two molecules (E alpha dE beta d and E alpha kE beta s) were associated with a T cell response to a nonmalarial epitope(s) carboxyterminal to the malaria sequence and encoded by a tetracycline resistance gene, read out of frame. If an analogous situation applies in humans, natural boosting by sporozoites will be very restricted. This has serious implications for the effectiveness of the vaccine, since constant high levels of antisporozoite antibodies and possibly antibody-independent T cell effector functions are required for immunity.

Cytotoxic T cells recognize a peptide from the circumsporozoite protein on malaria-infected hepatocytes.

Irradiated malaria sporozoites can induce CD8+ T cells that are required for protection against infection. However, the parasite antigens targeted by this immune response are unknown. We have discovered a 16-amino acid epitope from the Plasmodium yoelii circumsporozoite (CS) protein that is recognized by cytotoxic T cells from immune mice. Lymphocytes stimulated with this peptide can kill P. yoelii liver stage parasites in vitro in an MHC-restricted, antigen-specific manner. Thus, epitopes from the CS protein are presented on the surface of infected hepatocytes and can be targets for T cells, even though intact CS protein has not been detected on the surface of the infected hepatocyte. A vaccine that induced CTL to parasite antigens might protect humans against malaria by eliminating liver stage parasites.

Genetic correlations between measures of Mycobacterium bovis infection and economically important traits in Irish Holstein-Friesian dairy cows.

Mycobacterium bovis is the primary agent of tuberculosis (TB) in cattle. The failure of Ireland and some other countries to reach TB-free status indicates a need to investigate complementary control strategies. One such approach would be genetic selection for increased resistance to TB. Previous research has shown that considerable genetic variation exists for susceptibility to the measures of M. bovis infection, confirmed M. bovis infection, and M. bovis-purified protein derivative (PPD) responsiveness. The objective of this study was to estimate the genetic and phenotypic correlations between economically important traits and these measures of M. bovis infection. A total of 20,148 and 17,178 cows with confirmed M. bovis infection and M. bovis-PPD responsiveness records, respectively, were available for inclusion in the analysis. First- to third-parity milk, fat, and protein yields, somatic cell count, calving interval, and survival, as well as first-parity body condition score records, were available on cows that calved between 1985 and 2007. Bivariate linear-linear and threshold-linear sire mixed models were used to estimate (co)variance components. The genetic correlations between economically important traits and the measures of M. bovis infection estimated from the linear-linear and threshold-linear sire models were similar. The genetic correlations between susceptibility to confirmed M. bovis infection and economically important traits investigated in this study were all close to zero. Mycobacterium bovis-PPD responsiveness was positively genetically correlated with fat production (0.39) and body condition score (0.36), and negatively correlated with somatic cell score (-0.34) and survival (-0.62). Hence, selection for increased survival may indirectly reduce susceptibility to M. bovis infection, whereas selection for reduced somatic cell count and increased fat production and body condition score may increase susceptibility to M. bovis infection.

Evidence of genetic resistance of cattle to infection with Mycobacterium bovis.

Anecdotal evidence points to genetic variation in resistance of cattle to infection with Mycobacterium bovis, the causative agent of bovine tuberculosis (BTB), and published experimental evidence in deer and cattle suggests significant genetic variation in resistance and reactivity to diagnostic tests. However, such genetic variation has not been properly quantified in the United Kingdom dairy cattle population; it is possible that it exists and may be a factor influencing the occurrence of BTB. Using models based on the outcome of the process of diagnosis (ultimate fate models) and on the outcome of a single stage of diagnosis (continuation ratio models, herd test-date models), this study shows that there is heritable variation in individual cow susceptibility to BTB, and that selection for milk yield is unlikely to have contributed to the current epidemic. Results demonstrate that genetics could play an important role in controlling BTB by reducing both the incidence and the severity of herd breakdowns.

Performance of guinea fowl fed hevea seed meal or cashew nut meal as a partial substitute for soya bean meal.

Guinea fowl production is increasing in developing countries and has a crucial role in the fight against poverty. However, the feed cost is very high, especially the soya bean meal cost, and farmers cannot afford to buy commercial feed. Consequently, animals do not receive feed adapted to their nutritional needs and they exhibit poor performance. The aim of this paper is to partially substitute soya bean meal by local by-products, discarded, in abundant supply and not used in human nutrition. French Galor guinea fowl (Numida meleagris) and local African guinea fowl (150 birds per breed) were reared for 16 weeks and fed the same starter diet for the initial 4 weeks. From 4 weeks of age, experimental birds from each breed were randomly assigned to three grower isoproteic and isolipidic dietary treatments, each containing five replications (floor pens); each replication included 10 birds of the same breed. The guinea fowl of each breed were fed either control grower diet using soya bean meal as the protein supplement GS, or trial grower diet GN (soya bean meal supplement partially substituted by 15% cashew nut (Anacardium occidentale) meal) or trial grower diet GH (soya bean meal supplement partially substituted by 15% hevea seed (Hevea brasiliensis) meal). The results indicated that hevea seed meal contained a high content of n-3 polyunsaturated fatty acids (PUFAs) (21.2% of total fatty acids (FAs)). The use of hevea seed meal in guinea fowl grower diet was found to exert no adverse effect on growth performance and carcass yield. However, the use of cashew nut meal led to negative effects on performance like daily weight gain and feed conversion ratio. Therefore, cashew nut meal cannot be considered as a suitable partial substitute for soya bean meal in diets. The use of hevea seed meal led to a very low abdominal fat proportion and low blood triglyceride and cholesterol content. Additionally, inclusion of dietary hevea seed meal resulted in guinea fowl meat enriched in PUFAs, especially n-3 FAs, thereby significantly improving the nutritional value.

Effect of Hevea brasiliensis seed meal or Euphorbia heterophylla seed supplemented diets on performance, physicochemical and sensory properties of eggs, and egg yolk fatty acid profile in guinea fowl (Numida meleagris).

A total of 144 French selected breed (Galor) female guinea fowl (GF) of 42 wk of age were enrolled for a feeding trial of 15, 30, and 45 D duration. The birds were randomly assigned to 18 cages, each containing 8 birds. A total of 3 isonitrogenous and isocaloric dietary treatments were trialed, each diet comprising 6 replications (cages), which meant a total of 48 birds per diet. The GF were fed either a control diet C (commercial diet "FACI ponte 20", SIPRA, Ivory Coast, usually used for all poultry species) or the diet C supplemented with 5% Euphorbia heterophylla seeds (diet E) and the diet C supplemented with 5% Hevea seed meal (Hevea brasiliensis) (diet H). Animal performance were assessed for 3 periods (days 0 to 15, 0 to 30, and 0 to 45), and egg quality and composition were assessed at 15, 30, and 45 D of the trial. The results indicated no mortality during the trial. The laying rate was the highest (43.9%) with diet E and the lowest with diet C (32.5%), the laying rate with diet H being intermediate (38.5%). Diet E containing Euphorbia seeds led to a reduced cholesterol content of the eggs. Additionally, inclusion of Euphorbia seeds and, to a lesser extent, of the Hevea seed meal in the diet led to n-3 polyunsaturated fatty acid enriched GF eggs, with thereby, improved nutritional value. A sensory test did not find any difference between the 3 diets on trial.

A randomised controlled study shows supplementation of overweight and obese adults with lactobacilli and bifidobacteria reduces bodyweight and improves well-being.

In an exploratory, block-randomised, parallel, double-blind, single-centre, placebo-controlled superiority study (ISRCTN12562026, funded by Cultech Ltd), 220 Bulgarian participants (30 to 65 years old) with BMI 25-34.9 kg/m2 received Lab4P probiotic (50 billion/day) or a matched placebo for 6 months. Participants maintained their normal diet and lifestyle. Primary outcomes were changes in body weight, BMI, waist circumference (WC), waist-to-height ratio (WtHR), blood pressure and plasma lipids. Secondary outcomes were changes in plasma C-reactive protein (CRP), the diversity of the faecal microbiota, quality of life (QoL) assessments and the incidence of upper respiratory tract infection (URTI). Significant between group decreases in body weight (1.3 kg, p < 0.0001), BMI (0.045 kg/m2, p < 0.0001), WC (0.94 cm, p < 0.0001) and WtHR (0.006, p < 0.0001) were in favour of the probiotic. Stratification identified greater body weight reductions in overweight subjects (1.88%, p < 0.0001) and in females (1.62%, p = 0.0005). Greatest weight losses were among probiotic hypercholesterolaemic participants (-2.5%, p < 0.0001) alongside a significant between group reduction in small dense LDL-cholesterol (0.2 mmol/L, p = 0.0241). Improvements in QoL and the incidence rate ratio of URTI (0.60, p < 0.0001) were recorded for the probiotic group. No adverse events were recorded. Six months supplementation with Lab4P probiotic resulted in significant weight reduction and improved small dense low-density lipoprotein-cholesterol (sdLDL-C) profiles, QoL and URTI incidence outcomes in overweight/obese individuals.

The role of the hippocampus in mnemonic integration and retrieval: complementary evidence from lesion and inactivation studies.

Two forms of account have been proposed for how animals form integrated memories for patterns of stimulation: the elemental account holds that the elements that make up the pattern become directly linked to one another, whereas the configural account holds that these elements become bound together through their capacity to activate a separate, shared configural memory. The hippocampus and perirhinal cortex have been linked to both elemental and configural processes. Here, we assessed the role of the rat hippocampus and perirhinal cortex in these distinct ways of processing patterns of sensory stimulation involving auditory, visual context and temporal information. Using selective lesions and inactivation techniques we identified a specific role for the hippocampus in the retrieval of configural memories but not of those that could be encoded elementally; we also identified a role for the rat perirhinal cortex in visual contextual learning. These results, using a novel combination of behavioural assays, provide clear support for the view that patterns of stimulation can be encoded either elementally or configurally, and that disruption of hippocampal function leaves rats reliant on elemental processes.

Malaria pathogenesis.

Malaria is a disease caused by repeated cycles of growth of the parasite Plasmodium in the erythrocyte. Various cellular and molecular strategies allow the parasite to evade the human immune response for many cycles of parasite multiplication. Under certain circumstances Plasmodium infection causes severe anemia or cerebral malaria; the expression of disease is influenced by both parasite and host factors, as exemplified by the exacerbation of disease during pregnancy. This article provides an overview of malaria pathogenesis, synthesizing the recent field, laboratory, and epidemiological data that will lead to the development of strategies to reduce mortality and morbidity.

Research toward malaria vaccines.

Malaria exacts a toll of disease to people in the Tropics that seems incomprehensible to those only familiar with medicine and human health in the developed world. The methods of molecular biology, immunology, and cell biology are now being used to develop an antimalarial vaccine. The Plasmodium parasites that cause malaria have many stages in their life cycle. Each stage is antigenically distinct and potentially could be interrupted by different vaccines. However, achieving complete protection by vaccination may require a better understanding of the complexities of B- and T-cell priming in natural infections and the development of an appropriate adjuvant for use in humans.

Limited immunological recognition of critical malaria vaccine candidate antigens.

Current vaccine development strategies for malaria depend on widespread immunological responsiveness to candidate antigens such as the zygote surface antigens and the sporozoite coat protein, the circumsporozoite (CS) protein. Since immunological responsiveness is controlled mainly by genes mapping within the major histocompatibility complex (MHC), the humoral immune response to the zygote surface antigens and the cytotoxic T lymphocyte (CTL) response to the CS protein were examined in MHC-disparate congenic mouse strains. Only two of six strains responded to the 230-kilodalton zygote surface antigen and another two strains responded to the 48/45-kilodalton surface antigen. From two mouse strains, expressing between them five different class I MHC molecules, there was recognition of only a single CTL epitope from the CS protein, which was from a polymorphic segment of the molecule. The restricted CTL response to this protein parallels the restricted antibody response to this protein observed in humans and mice. These findings suggest that subunit malaria vaccines now being developed may be ineffective.

Construction of synthetic immunogen: use of new T-helper epitope on malaria circumsporozoite protein.

The circumsporozoite (CS) protein of Plasmodium falciparum is the focus of intense efforts to develop an antisporozoite malaria vaccine. Localization of sites for T-cell recognition on this molecule is critical for vaccine design. By using an algorithm designed to predict T-cell sites and a large panel of H-2 congenic mice, a major nonrepetitive T-cell site was located. When a synthetic peptide corresponding to this site was covalently linked to the major B-cell site on the molecule, an immunogen capable of eliciting a high-titer antibody response was formed. This peptide sequence could prime helper T cells for a secondary response to the intact CS protein. The new helper T-cell site is located outside the repetitive region of the CS protein and appears to be the immunodominant T site on the molecule. This approach should be useful in the rational design and construction of vaccines.