Investigation of the link between avian vacuolar myelinopathy and a novel species of cyanobacteria through laboratory feeding trials

Avian vacuolar myelinopathy (AVM) is a neurologic disease affecting Bald Eagles (Haliaeetus leucocephalus), American Coots (Fulica americana), and other birds in the southeastern United States. The cause of the disease has not yet been determined, although it is generally thought to be a natural toxin. Previous studies have linked AVM to aquatic vegetation, and the current working hypothesis is that a species of cyanobacteria growing epiphytically on that vegetation is producing a toxin that causes AVM. Surveys of epiphytic communities have identified a novel species of cyanobacteria in the order Stigonematales as the most likely suspect. The purpose of this study was to further examine the relationship between the suspect Stigonematales species and induction of AVM, by using animal feeding trials. Adult Mallards and domestic chickens were fed aquatic vegetation from two study sites containing the suspect cyanobacterial epiphyte, as well as a control site that did not contain the Stigonematales species. Two trials were conducted. The first trial used vegetation collected during mid-October 2003, and the second trial used vegetation collected during November and December 2003. Neither treatment nor control birds in the first trial developed AVM lesions. Ten of 12 treatment Mallards in the second trial were diagnosed with AVM, and control birds were not affected. This study provides further evidence that the novel Stigonematales species may be involved with AVM induction, or at the least it is a good predictor of AVM toxin presence in a system. The results also demonstrate the seasonal nature of AVM events.     

Novel malonamide derivatives as potent kappa opioid receptor agonists

A novel series of malonamide derivatives was synthesized. These amides were shown to be potent and selective kappa opioid receptor agonists.     

Does soil type drive social organization in southern hairy‐nosed wombats?

Spatiotemporal distributions of key resources are hypothesized to underpin sociobiological patterns. Burrow availability and quality is of paramount importance to fossorial animals. The southern hairy-nosed wombat (Lasiorhinus latifrons) burrows in both hard and friable soils. Theoretical and empirical studies suggest that the harder substrate should promote closer geographical clustering of burrows than in softer soils. Clustered burrows are expected to be associated with larger group sizes. If sociality is driven by constraint rather than advantage, patterns of spatial and temporal distribution of animals within and among groups may show indications of avoidance or even antagonism, and 'making the best of a bad job' via positive kin associations to offset the disadvantages of high-density living. To test these ideas, we compared warren relatedness and social structure of L. latifrons on friable soils (Nullarbor Plain) and hard calcrete (Brookfield Conservation Park, BCP). Individuals were sampled by noninvasive collection of hairs for genotyping to identify individuals and to estimate their space-use and associative behaviour with respect to relatedness. Burrows in calcrete were indeed more clumped, and warren and group size larger. Differences in spatiotemporal organization and relatedness structure between sites were in the expected direction: (i) Nullarbor males associated and shared warrens less than at BCP; and (ii) Nullarbor spatial relatedness patterning data were not consistent with proposed female breeding dispersal, in contrast to those at BCP. Under Nullarbor (low density) conditions, cooperation or tolerance between males may be less advantageous, and accessing or digging burrows should be less of a constraint for juvenile females.     

Shade as enrichment: testing preferences for shelter in two model fish species

We compared preferences shown by zebrafish Danio rerio and three-spined stickleback Gasterosteus aculeatus for shelter provided by above-tank shade and artificial plants. Zebrafish showed no preference for either shelter, whereas sticklebacks showed a preference for both shelter types over open areas and for shade over plants. Our results suggest shade may be used as enrichment for captive fish and re-emphasise the importance of species-specific welfare considerations.     

Use of Bacteroidales Microbial Source Tracking To Monitor Fecal Contamination in Fresh Produce Production

In recent decades, fresh and minimally processed produce items have been associated with an increasing proportion of food-borne illnesses. Most pathogens associated with fresh produce are enteric (fecal) in origin, and contamination can occur anywhere along the farm-to-fork chain. Microbial source tracking (MST) is a tool developed in the environmental microbiology field to identify and quantify the dominant source(s) of fecal contamination. This study investigated the utility of an MST method based on Bacteroidales 16S rRNA gene sequences as a means of identifying potential fecal contamination, and its source, in the fresh produce production environment. The method was applied to rinses of fresh produce, source and irrigation waters, and harvester hand rinses collected over the course of 1 year from nine farms (growing tomatoes, jalapeño peppers, and cantaloupe) in Northern Mexico. Of 174 samples, 39% were positive for a universal Bacteroidales marker (AllBac), including 66% of samples from cantaloupe farms (3.6 log₁₀ genome equivalence copies [GEC]/100 ml), 31% of samples from tomato farms (1.7 log₁₀ GEC/100 ml), and 18% of samples from jalapeño farms (1.5 log₁₀ GEC/100 ml). Of 68 AllBac-positive samples, 46% were positive for one of three human-specific markers, and none were positive for a bovine-specific marker. There was no statistically significant correlation between Bacteroidales and generic Escherichia coli across all samples. This study provides evidence that Bacteroidales markers may serve as alternative indicators for fecal contamination in fresh produce production, allowing for determination of both general contamination and that derived from the human host.     

Assessment of Humoral Immune Responses to Blood-Stage Malaria Antigens following ChAd63-MVA Immunization,Controlled Human Malaria Infection and Natural Exposure

The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite – MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors – ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI) with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i) ChAd63-MVA immunization, ii) immunization and CHMI, and iii) primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i) total IgG responses before and after CHMI, ii) responses to allelic variants of MSP1 and AMA1, iii) functional growth inhibitory activity (GIA), iv) IgG avidity, and v) isotype responses (IgG1-4, IgA and IgM). These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other diseases targets, these data should help to guide further immuno-monitoring studies of vaccine-induced human antibody responses.     

Association between Cytomegalovirus Antibody Levels and Cognitive Functioning in Non-Elderly Adults

Background

Elevated levels of antibodies to Cytomegalovirus (CMV) have been associated with cognitive impairment, but the quantitative relationship between CMV antibody levels and domains of cognitive functioning in younger adults has not been established.

Methods

We measured IgG class antibodies to Cytomegalovirus in 521 individuals, mean age 32.8 years. Participants were selected for the absence of psychiatric disorder and of a serious medical condition that could affect brain functioning. Cognitive functioning was measured with the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the Wisconsin Card Sorting Test, Trail Making Test part A, and the WAIS III Letter Number Sequencing subtest. Linear regression analyses were used to measure the quantitative association between cognitive scores and Cytomegalovirus IgG antibody level. Logistic regression analyses were used to measure the odds of low cognitive scores and elevated antibody levels defined as an antibody level > = 50^th, 75^th, and 90^th percentile of the group.

Results

Higher levels of CMV antibodies were associated with lower performance on RBANS Total (coefficient −1.03, p<.0002), Delayed Memory (coefficient −0.94, p<.001), Visuospatial/Constructional (coefficient −1.77, p<5×10⁻⁷), and Letter Number Sequencing (coefficient −0.15, p<.03). There was an incremental relationship between the level of CMV antibody elevation and the odds of a low RBANS Total score. The odds of a low total cognitive score were 1.63 (95^th % CI 1.01, 2.64; p<.045), 2.22 (95^th % CI 1.33, 3.70; p<.002), and 2.46 (95^th % CI 1.24, 4.86; p<.010) with a CMV antibody level greater than or equal to the 50^th, 75^th, and 90^th percentile respectively.

Conclusions

Higher levels of Cytomegalovirus antibodies are associated with lower levels of cognitive functioning in non-elderly adults. Methods for the prevention and treatment of CMV infection should be evaluated to determine if they result in an improvement in cognitive functioning in otherwise healthy adults.