Environmental,geographical and time-related impacts on avian malaria infections in native and introduced populations of house sparrows (Passer domesticus), a globally invasive species

Aim

The increasing spread of vector-borne diseases has resulted in severe health concerns for humans, domestic animals and wildlife, with changes in land use and the introduction of invasive species being among the main possible causes for this increase. We explored several ecological drivers potentially affecting the local prevalence and richness of avian malaria parasite lineages in native and introduced house sparrows (Passer domesticus) populations.

Location

Global.

Time period

2002–2019.

Major taxa studied

Avian Plasmodium parasites in house sparrows.

Methods

We analysed data from 2,220 samples from 69 localities across all continents, except Antarctica. The influence of environment (urbanization index and human density), geography (altitude, latitude, hemisphere) and time (bird breeding season and years since introduction) were analysed using generalized additive mixed models (GAMMs) and random forests.

Results

Overall, 670 sparrows (30.2%) were infected with 22 Plasmodium lineages. In native populations, parasite prevalence was positively related to urbanization index, with the highest prevalence values in areas with intermediate urbanization levels. Likewise, in introduced populations, prevalence was positively associated with urbanization index; however, higher infection occurred in areas with either extreme high or low levels of urbanization. In introduced populations, the number of parasite lineages increased with altitude and with the years elapsed since the establishment of sparrows in a new locality. Here, after a decline in the number of parasite lineages in the first 30 years, an increase from 40 years onwards was detected.

Main conclusions

Urbanization was related to parasite prevalence in both native and introduced bird populations. In invaded areas, altitude and time since bird introduction were related to the number of Plasmodium lineages found to be infecting sparrows.     

Genetic and functional analyses of SHANK2 mutations suggest a multiple hit model of autism spectrum disorders

Autism spectrum disorders (ASD) are a heterogeneous group of neurodevelopmental disorders with a complex inheritance pattern. While many rare variants in synaptic proteins have been identified in patients with ASD, little is known about their effects at the synapse and their interactions with other genetic variations. Here, following the discovery of two de novo SHANK2 deletions by the Autism Genome Project, we identified a novel 421 kb de novo SHANK2 deletion in a patient with autism. We then sequenced SHANK2 in 455 patients with ASD and 431 controls and integrated these results with those reported by Berkel et al. 2010 (n = 396 patients and n = 659 controls). We observed a significant enrichment of variants affecting conserved amino acids in 29 of 851 (3.4%) patients and in 16 of 1,090 (1.5%) controls (P = 0.004, OR = 2.37, 95% CI = 1.23–4.70). In neuronal cell cultures, the variants identified in patients were associated with a reduced synaptic density at dendrites compared to the variants only detected in controls (P = 0.0013). Interestingly, the three patients with de novo SHANK2 deletions also carried inherited CNVs at 15q11–q13 previously associated with neuropsychiatric disorders. In two cases, the nicotinic receptor CHRNA7 was duplicated and in one case the synaptic translation repressor CYFIP1 was deleted. These results strengthen the role of synaptic gene dysfunction in ASD but also highlight the presence of putative modifier genes, which is in keeping with the “multiple hit model” for ASD. A better knowledge of these genetic interactions will be necessary to understand the complex inheritance pattern of ASD.     

The x cystine/glutamate antiporter (xCT) as a potential target for therapy of cancer: Yet another cytotoxic anticancer approach?

This article was published online on 4 May 2009. An error was subsequently identified. This notice is included in the online and print versions to indicate that both have been corrected 8 June 2009.     

In vitro and ex vivo evaluation of second-generation histone deacetylase inhibitors for the treatment of spinal muscular atrophy

Among a panel of histone deacetylase (HDAC) inhibitors investigated, suberoylanilide hydroxamic acid (SAHA) evolved as a potent and non-toxic candidate drug for the treatment of spinal muscular atrophy (SMA), an alpha-motoneurone disorder caused by insufficient survival motor neuron (SMN) protein levels. SAHA increased SMN levels at low micromolar concentrations in several neuroectodermal tissues, including rat hippocampal brain slices and motoneurone-rich cell fractions, and its therapeutic capacity was confirmed using a novel human brain slice culture assay. SAHA activated survival motor neuron gene 2 (SMN2), the target gene for SMA therapy, and inhibited HDACs at submicromolar doses, providing evidence that SAHA is more efficient than the HDAC inhibitor valproic acid, which is under clinical investigation for SMA treatment. In contrast to SAHA, the compounds m-Carboxycinnamic acid bis-Hydroxamide, suberoyl bishydroxamic acid and M344 displayed unfavourable toxicity profiles, whereas MS-275 failed to increase SMN levels. Clinical trials have revealed that SAHA, which is under investigation for cancer treatment, has a good oral bioavailability and is well tolerated, allowing in vivo concentrations shown to increase SMN levels to be achieved. Because SAHA crosses the blood-brain barrier, oral administration may allow deceleration of progressive alpha-motoneurone degeneration by epigenetic SMN2 gene activation.     

Distinct genetic groups of Giardia intestinalis distinguished by restriction fragment length polymorphisms.

The taxonomic status of the parasitic protozoal species Giardia intestinalis depends on the morphological similarity of all Giardia isolated from humans and the presumption that Giardia are host-specific. On the basis of electrophoretic data derived from examination of 26 enzyme loci in Australian isolates, it has been proposed that G. intestinalis is a species complex comprising three or four genetically distinct (but morphologically cryptic) species. These received the tentative designations of genetic groups I-IV (R. H. Andrews, M. Adams, P. F. L. Boreham, G. Mayrhofer & B. P. Meloni. International Journal for Parasitology 19, 183-190, 1989). In the present study, two unrelated DNA probes (one specific for a gene encoding a trophozoite surface protein, the other detecting a non-coding repetitive sequence within the G. intestinalis genome) were used in Southern hybridization analyses to examine 10 axenic isolates of G. intestinalis, established from diverse geographical regions in Australia, together with the Portland-1 isolate from the USA. Both probes identified every isolate unambiguously as belonging to one or other of two genetic clusters. Electrophoretic analysis of the same samples indicated that these clusters correspond to the previously defined genetic groups I and II. No heterogeneity was apparent within the seven group I isolates using either probe. However, when probed with the repetitive sequence, the four isolates belonging to group II exhibited small differences in banding patterns, suggesting that this group may be less homogeneous than group I.(ABSTRACT TRUNCATED AT 250 WORDS)     

Alternative pathway activation of complement by a murine parasitic nematode (Nematospiroides dubius)

The cuticular surface of the infectious third-stage larvae of Nematospiroides dubius activates complement via the alternative pathway. Sensitisation of larvae with complement or with antibodies from the serum of immune mice (resistant to reinfection) promoted the adherence of mouse peritoneal exudate cells to the larval cuticle during incubation in vitro. The infectivity of larvae sensitized with antibody or complement was significantly reduced after incubation with cells from immune mice.     

Improving the Extent of Malignant Glioma Resection by Dual Intraoperative Visualization Approach

Despite continuing debates around cytoreductive surgery in malignant gliomas, there is broad consensus that increased extent of tumor reduction improves overall survival. However, maximization of the extent of tumor resection is hampered by difficulty in intraoperative discrimination between normal and pathological tissue. In this context, two established methods for tumor visualization, fluorescence guided surgery with 5-ALA and intraoperative MRI (iMRI) with integrated functional neuronavigation were investigated as a dual intraoperative visualization (DIV) approach. Thirty seven patients presumably suffering from malignant gliomas (WHO grade III or IV) according to radiological appearance were included. Twenty-one experimental sequences showing complete resection according to the 5-ALA technique were confirmed by iMRI. Fourteen sequences showing complete resection according to the 5-ALA technique could not be confirmed by iMRI, which detected residual tumor. Further analysis revealed that these sequences could be classified as functional grade II tumors (adjacent to eloquent brain areas). The combination of fluorescence guided resection and intraoperative evaluation by high field MRI significantly increased the extent of tumor resection in this subgroup of malignant gliomas located adjacent to eloquent areas from 61.7% to 100%; 5-ALA alone proved to be insufficient in attaining gross total resection without the danger of incurring postoperative neurological deterioration. Furthermore, in the case of functional grade III gliomas, iMRI in combination with functional neuronavigation was significantly superior to the 5-ALA resection technique. The extent of resection could be increased from 57.1% to 71.2% without incurring postoperative neurological deficits.     

Use of random amplified polymorphic DNA (RAPD) analysis for the identification of Giardia intestinalis subtypes and phylogenetic tree construction

A comparison of random amplified polymorphic DNA (RAPD) was used to investigate genetic polymorphisms among 25 isolates of Giardia intestinalis and to assess the utility of RAPD for subtype detection and genealogical analysis. Using data obtained for six human and 19 animal-derived isolates in polymerase chain reactions using 13 different primers, phylogenetic trees were constructed and bootstrap values computed by the program FreeTree. Three major clades were distinguished, corresponding to previously defined genetic assemblages A, B, and E. The purported specificity of assemblage E genotypes for artiodactyl hosts was supported. Assemblages A and B showed wide host spectra, including human and animal hosts. No correlation was found between the genotype of analyzed isolates and the presence or absence of the double-stranded RNA Giardiavirus. The results indicate that RAPD data provide reliable genetic information that can be used for both "fingerprinting" and genealogical purposes.     

Adult male mice emit context-specific ultrasonic vocalizations that are modulated by prior isolation or group rearing environment

Social interactions in mice are frequently analysed in genetically modified strains in order to get insight of disorders affecting social interactions such as autism spectrum disorders. Different types of social interactions have been described, mostly between females and pups, and between adult males and females. However, we recently showed that social interactions between adult males could also encompass cognitive and motivational features. During social interactions, rodents emit ultrasonic vocalizations (USVs), but it remains unknown if call types are differently used depending of the context and if they are correlated with motivational state. Here, we recorded the calls of adult C57BL/6J male mice in various behavioral conditions, such as social interaction, novelty exploration and restraint stress. We introduced a modulator for the motivational state by comparing males maintained in isolation and males maintained in groups before the experiments. Male mice uttered USVs in all social and non-social situations, and even in a stressful restraint context. They nevertheless emitted the most important number of calls with the largest diversity of call types in social interactions, particularly when showing a high motivation for social contact. For mice maintained in social isolation, the number of calls recorded was positively correlated with the duration of social contacts, and most calls were uttered during contacts between the two mice. This correlation was not observed in mice maintained in groups. These results open the way for a deeper understanding and characterization of acoustic signals associated with social interactions. They can also help evaluating the role of motivational states in the emission of acoustic signals.