Antibody-based immunotherapy in high-risk neuroblastoma

Although great advances have been made in the treatment of low- and intermediate-risk neuroblastoma in recent years, the prognosis for advanced disease remains poor. Therapies based on monoclonal antibodies that specifically target tumour cells have shown promise for treatment of high-risk neuroblastoma. This article reviews the use of monoclonal antibodies either as monotherapy or as part of a multifaceted treatment approach for advanced neuroblastoma, and explains how toxins, cytokines, radioactive isotopes or chemotherapeutic drugs can be conjugated to antibodies to enhance their effects. Tumour resistance, the development of blocking antibodies, and other problems hindering the effectiveness of monoclonal antibodies are also discussed. Future therapies under investigation in the area of immunotherapy for neuroblastoma are considered.     

Synthesis and antiviral properties of aza-analogues of acyclovir

Aza-analogues of Acyclovir were obtained from N-(2-pivaloyloxyethyl)-N-(pivaloyloxymethyl)-p-toluenesulfonamide via a one-pot base silylation/nucleoside coupling procedure. The antiviral activities of all aza-nucleosides in vitro against a variety of viruses were evaluated. None of these compounds displayed any specific antiviral effects.     

Bioluminescence imaging of period1 gene expression in utero

The use of real-time reporters has accelerated our understanding of gene expression in vivo. This study examined the feasibility of a luciferase-based reporter to image spatiotemporal changes in fetal gene expression in utero. We chose to monitor Period1 (Per1) because it is expressed broadly in the body and plays a role in circadian rhythmicity. Using rats carrying a Per1::luc transgene, we repetitively imaged fetuses in utero throughout gestation. We found that bioluminescence was specific to transgenic pups, increased dramatically on embryonic day 10 (10 days after successful mating), and continued to increase logarithmically until birth. Diurnal fluctuations in Per1 expression were apparent several days prior to birth. These results demonstrate the feasibility of in utero imaging of mammalian gene expression, tracking of fetal gene expression from the same litter, and early detection of mammalian clock gene expression. We conclude that luciferase-based reporters can provide a sensitive, noninvasive measure of in utero gene expression.     

Shelter availability reduces the effects of the invasive Red Swamp Crayfish (Procambarus clarkii) on eelgrass-dominated clear-water lakes: a mesocosm approach

Hydrobiologia - Shelter availability is one of the key features governing crayfish habitat quality. It can directly influence crayfish’s individual survival of by lowering the risk of...     

Failed protective effort of ex situ conservation of River Vistula trout (Salmo trutta) in Sweden

Environmental Biology of Fishes - Ex situ conservation comprises some of the oldest and best-known conservation methods and it has been applied for different fish stocks. This study describes...     

Linked genetic variants on chromosome 10 control ear morphology and body mass among dog breeds

Background

The domestic dog is a rich resource for mapping the genetic components of phenotypic variation due to its unique population history involving strong artificial selection. Genome-wide association studies have revealed a number of chromosomal regions where genetic variation associates with morphological characters that typify dog breeds. A region on chromosome 10 is among those with the highest levels of genetic differentiation between dog breeds and is associated with body mass and ear morphology, a common motif of animal domestication. We characterised variation in this region to uncover haplotype structure and identify candidate functional variants.

Results

We first identified SNPs that strongly associate with body mass and ear type by comparing sequence variation in a 3 Mb region between 19 breeds with a variety of phenotypes. We next genotyped a subset of 123 candidate SNPs in 288 samples from 46 breeds to identify the variants most highly associated with phenotype and infer haplotype structure. A cluster of SNPs that associate strongly with the drop ear phenotype is located within a narrow interval downstream of the gene MSRB3, which is involved in human hearing. These SNPs are in strong genetic linkage with another set of variants that correlate with body mass within the gene HMGA2, which affects human height. In addition we find evidence that this region has been under selection during dog domestication, and identify a cluster of SNPs within MSRB3 that are highly differentiated between dogs and wolves.

Conclusions

We characterise genetically linked variants that potentially influence ear type and body mass in dog breeds, both key traits that have been modified by selective breeding that may also be important for domestication. The finding that variants on long haplotypes have effects on more than one trait suggests that genetic linkage can be an important determinant of the phenotypic response to selection in domestic animals.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1702-2) contains supplementary material, which is available to authorized users.