Does avian malaria reduce fledging success: an experimental test of the selection hypothesis

Like many parasites, avian haematozoa are often found at lower infection intensities in older birds than young birds. One explanation, known as the “selection” hypothesis, is that infected young birds die before reaching adulthood, thus removing the highest infection intensities from the host population. We tested this hypothesis in the field by experimentally infecting nestling rock pigeons (Columba livia) with the malaria parasite Haemoproteus columbae. We compared the condition and fledging success of infected nestlings to that of uninfected controls. There was no significant difference in the body mass, fledging success, age at fledging, or post-fledging survival of experimental versus control birds. These results were unexpected, given that long-term studies of older pigeons have demonstrated chronic effects of H. columbae. We conclude that H. columbae has little impact on nestling pigeons, even when they are directly infected with the parasite. Our study provides no support for the selection hypothesis that older birds have lower parasite loads because parasites are removed from the population by infected nestlings dying. To our knowledge, this is the first study to test the impact of avian malaria using experimental inoculations under natural conditions.     

Massively Parallel Sequencing Reveals the Complex Structure of an Irradiated Human Chromosome on a Mouse Background in the Tc1 Model of Down Syndrome

Down syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and presents a complex phenotype that arises from abnormal dosage of genes on this chromosome. However, the individual dosage-sensitive genes underlying each phenotype remain largely unknown. To help dissect genotype – phenotype correlations in this complex syndrome, the first fully transchromosomic mouse model, the Tc1 mouse, which carries a copy of human chromosome 21 was produced in 2005. The Tc1 strain is trisomic for the majority of genes that cause phenotypes associated with DS, and this freely available mouse strain has become used widely to study DS, the effects of gene dosage abnormalities, and the effect on the basic biology of cells when a mouse carries a freely segregating human chromosome. Tc1 mice were created by a process that included irradiation microcell-mediated chromosome transfer of Hsa21 into recipient mouse embryonic stem cells. Here, the combination of next generation sequencing, array-CGH and fluorescence in situ hybridization technologies has enabled us to identify unsuspected rearrangements of Hsa21 in this mouse model; revealing one deletion, six duplications and more than 25 de novo structural rearrangements. Our study is not only essential for informing functional studies of the Tc1 mouse but also (1) presents for the first time a detailed sequence analysis of the effects of gamma radiation on an entire human chromosome, which gives some mechanistic insight into the effects of radiation damage on DNA, and (2) overcomes specific technical difficulties of assaying a human chromosome on a mouse background where highly conserved sequences may confound the analysis. Sequence data generated in this study is deposited in the ENA database, Study Accession number: ERP000439.     

The Detection of Novelty Relies on Dopaminergic Signaling: Evidence from Apomorphine's Impact on the Novelty N2

Despite much research, it remains unclear if dopamine is directly involved in novelty detection or plays a role in orchestrating the subsequent cognitive response. This ambiguity stems in part from a reliance on experimental designs where novelty is manipulated and dopaminergic activity is subsequently observed. Here we adopt the alternative approach: we manipulate dopamine activity using apomorphine (D1/D2 agonist) and measure the change in neurological indices of novelty processing. In separate drug and placebo sessions, participants completed a von Restorff task. Apomorphine speeded and potentiated the novelty-elicited N2, an Event-Related Potential (ERP) component thought to index early aspects of novelty detection, and caused novel-font words to be better recalled. Apomorphine also decreased the amplitude of the novelty-P3a. An increase in D1/D2 receptor activation thus appears to potentiate neural sensitivity to novel stimuli, causing this content to be better encoded.     

Effects of Altered Light and Feeding Regimes on the Zooplankton Feeding Capability of Hydra viridis

The effects of light regime, feeding regime and tentacle number on the zooplankton feeding capability of Hydra viridis were tested in the laboratory. Feeding was measured by exposing Hydra to a known volume of Artemia salina nauplii and recording the number captured and ingested. In all cases there was a correlation between the number of Artemia captured and the number ingested. H. viridis with 7 tentacles captured and ingested more Artemia than Hydra with 6 tentacles. However, changes in light and/or feeding regimes did not alter the number of tentacles/Hydra. Varying light and feeding regimes altered the number of Zoochlorellae/cell and Hydra growth rate. There was no effect on the number of Artemia captured or ingested and no effect on the percent ingestion of captured Artemia. These data suggest that, under these conditions, zooplankton feeding by H. viridis is independent of nutritional history.     

In vitro replication of human mitochondrial DNA: accurate initiation at the origin of light-strand synthesis

Synthesis of human light-strand mitochondrial DNA was accomplished in vitro using DNA primase, DNA polymerase, and other accessory proteins isolated from human mitochondria. Replication begins with the synthesis of primer RNA on a T-rich sequence in the origin stem-loop structure of the template DNA and absolutely requires ATP. A transition from RNA synthesis to DNA synthesis occurs near the base of the stem-loop structure and a potential recognition site for signaling that transition has been identified. The start sites of the in vitro products were mapped at the nucleotide level and were found to be in excellent agreement with those of in vivo nascent light-strand DNA. Isolated human mitochondrial enzymes recognize and utilize the bovine, but not the mouse, origin of light-strand replication.     

Elasmobranch immune cells as a source of novel tumor cell inhibitors: Implications for public health

Reports that elasmobranchs (sharks, skates, and rays) may havea low incidence of disease have stimulated interest in understandingthe role of their immune system in this apparent resistance.Although research in this area may potentially translate intoapplications for human health, a basic understanding of theelasmobranch immune system components and how they functionis essential. As in higher vertebrates, elasmobranch fishespossess thymus and spleen, but in the absence of bone marrowand lymph nodes, these fish have evolved unique lymphomyeloidtissues, namely epigonal and Leydig organs. As conditions forshort-term culture of elasmobranch immune cells have becomebetter understood, the opportunity to examine functional activityof cytokine-like factors derived from conditioned culture mediumhas resulted in the identification of growth inhibitory activityagainst a variety of tumor cell lines. Specifically, the mediumenriched by short term culture of bonnethead shark (Sphyrnatiburo) epigonal cells (epigonal conditioned medium, ECM) hasbeen shown to inhibit the growth of mammalian tumor cell lines,including fibrosarcoma (WEHI-164), melanoma (A375.S2), B-celllymphoma (Daudi), T-cell leukemia (Jurkat), pancreatic cancer(PANC-1), ovarian cancer (NIH:OVCAR-3), and three breast carcinomacell lines (MCF7, HCC38, Hs578T). Of the cell lines tested,WEHI-164, A375.S2, Daudi, and Jurkat cells were among the mostsensitive to growth inhibitory activity of ECM whereas PANC-1and NIH:OVCAR-3 cells were among the least sensitive. In addition,ECM demonstrated preferential growth inhibition of malignantcells in assays against two different malignant/non-malignantcell line pairs (HCC38/HCC38 BL and Hs 578T/Hs 578Bst). Separationof protein components of ECM using SDS-PAGE resulted in a veryreproducible pattern of three major bands corresponding to molecularsizes of approximately 40–42 kD, 24 kD, and 17 kD. Activityis lost after heating at 75°C for 30 min, and can be diminishedby treatment with proteinase K and protease. Activity is notaffected by treating with trypsin, DNase I or RNase A.     

Uncovering genomic causes of co-morbidity in epilepsy: gene-driven phenotypic characterization of rare microdeletions

Background

Patients with epilepsy often suffer from other important conditions. The existence of such co-morbidities is frequently not recognized and their relationship with epilepsy usually remains unexplained.

Methodology/Principal Findings

We describe three patients with common, sporadic, non-syndromic epilepsies in whom large genomic microdeletions were found during a study of genetic susceptibility to epilepsy. We performed detailed gene-driven clinical investigations in each patient. Disruption of the function of genes in the deleted regions can explain co-morbidities in these patients.

Conclusions/Significance

Co-morbidities in patients with epilepsy can be part of a genomic abnormality even in the absence of (known) congenital malformations or intellectual disabilities. Gene-driven phenotype examination can also reveal clinically significant unsuspected condition.     

Detection of Lymphocytic Choriomeningitis Virus Antibody in Murine Sera by Immunofluorescence

An immunofluorescence technique developed for detection of antibody in murine sera to lymphocyitc choriomeningitis virus is described.