Graphs with two isomorphism classes of spanning unicyclic subgraphs

The graphs whose spanning unicyclic subgraphs partition into exactly two isomorphism classes are characterized.This work is a continuation of [6] where graphs with one isomorphism class of spanning unicyclic graphs are characterized. The analogous question for spanning trees was posed in [10] and graphs with one isomorphism class of spanning trees were characterized in [2], [3], [4], [7], [11] while graphs with two isomorphism classes of spanning trees were characterized in [4], [5]. Related topics are treated in [1], [8], [9].     

Antisense-mediated isoform switching of steroid receptor coactivator-1 in the central nucleus of the amygdala of the mouse brain

Background

Antisense oligonucleotide (AON)-mediated exon skipping is a powerful tool to manipulate gene expression. In the present study we investigated the potential of exon skipping by local injection in the central nucleus of the amygdala (CeA) of the mouse brain. As proof of principle we targeted the splicing of steroid receptor coactivator-1 (SRC-1), a protein involved in nuclear receptor function. This nuclear receptor coregulator exists in two splice variants (SRC-1a and SRC-1e) which display differential distribution and opposing activities in the brain, and whose mRNAs differ in a single SRC-1e specific exon.

Methods

For proof of principle of feasibility, we used immunofluorescent stainings to study uptake by different cell types, translocation to the nucleus and potential immunostimulatory effects at different time points after a local injection in the CeA of the mouse brain of a control AON targeting human dystrophin with no targets in the murine brain. To evaluate efficacy we designed an AON targeting the SRC-1e-specific exon and with qPCR analysis we measured the expression ratio of the two splice variants.

Results

We found that AONs were taken up by corticotropin releasing hormone expressing neurons and other cells in the CeA, and translocated into the cell nucleus. Immune responses after AON injection were comparable to those after sterile saline injection. A successful shift of the naturally occurring SRC-1a:SRC-1e expression ratio in favor of SRC-1a was observed, without changes in total SRC-1 expression.

Conclusions

We provide a proof of concept for local neuropharmacological use of exon skipping by manipulating the expression ratio of the two splice variants of SRC-1, which may be used to study nuclear receptor function in specific brain circuits. We established that exon skipping after local injection in the brain is a versatile and useful tool for the manipulation of splice variants for numerous genes that are relevant for brain function.     

A carbon nanotube structured biomimetic catalyst for polysaccharide degradation

A unique artificial catalyst that mimics the structure of active sites in real enzymes using functionalized carbon nanotubes is presented. This concept will allow for the potential construction of a library of biomimetic catalysts for enzyme active centers, for which the structure-catalysis relationships are well defined.