Fusion, fission, and scrambling of the bilaterian genome in Bryozoa.

Groups of orthologous genes are commonly found together on the same chromosome over vast evolutionary distances. This extensive physical gene linkage, known as macrosynteny, is seen between bilaterian phyla as divergent as Chordata, Echinodermata, Mollusca, and Nemertea. Here, we report a unique pattern of genome evolution in Bryozoa, an understudied phylum of colonial invertebrates.

Annelid Comparative Genomics and the Evolution of Massive Lineage-Specific Genome Rearrangement in Bilaterians.

The organization of genomes into chromosomes is critical for processes such as genetic recombination, environmental adaptation, and speciation. All animals with bilateral symmetry inherited a genome structure from their last common ancestor that has been highly conserved in some taxa but seemingly unconstrained in others. However, the evolutionary forces driving these differences and the processes by which they emerge have remained largely uncharacterized.

Predicting Radiotherapy Patient Outcomes with Real-Time Clinical Data Using Mathematical Modelling.

Longitudinal tumour volume data from head-and-neck cancer patients show that tumours of comparable pre-treatment size and stage may respond very differently to the same radiotherapy fractionation protocol. Mathematical models are often proposed to predict treatment outcome in this context, and have the potential to guide clinical decision-making and inform personalised fractionation protocols. Hindering effective use of models in this context is the sparsity of clinical measurements juxtaposed with the model complexity required to produce the full range of possible patient responses.

Rapid Evolution of the Embryonically Expressed Homeobox Gene LEUTX within Primates.

LEUTX is a homeodomain transcription factor expressed in the very early embryo with a function around embryonic genome activation. The LEUTX gene is found only in eutherian mammals including humans but, unlike the majority of homeobox genes, the encoded amino acid sequence is very different between divergent mammalian species. However, whether dynamic evolution has also occurred between closely related mammalian species remains unclear.

An Model of T Cell Infiltration Dynamics Based on an Advanced System to Enhance Preclinical Decision Making in Cancer Immunotherapy.

Cancer immunotherapy often involves the use of engineered molecules to selectively bind and activate T cells located within tumour tissue. Fundamental to the success of such treatments is the presence or recruitment of T cells localised within the tumour microenvironment. Advanced organ-on-a-chip systems provide an setting in which to investigate how novel molecules influence the spatiotemporal dynamics of T cell infiltration into tissue, both in the context of anti-tumour efficacy and off-tumour toxicity.

PRD-Class Homeobox Genes in Bovine Early Embryos: Function, Evolution, and Overlapping Roles.

Eutherian Totipotent Cell Homeobox (ETCHbox) genes are mammalian-specific PRD-class homeobox genes with conserved expression in the preimplantation embryo but fast-evolving and highly divergent sequences. Here, we exploit an ectopic expression approach to examine the role of bovine ETCHbox genes and show that ARGFX and LEUTX homeodomain proteins upregulate genes normally expressed in the blastocyst; the identities of the regulated genes suggest that, in vivo, the ETCHbox genes play a role in coordinating the physical formation of the blastocyst structure. Both genes also downregulate genes expressed earlier during development and genes associated with an undifferentiated cell state, possibly via the JAK/STAT pathway.

Dynamic Molecular Evolution of Mammalian Homeobox Genes: Duplication, Loss, Divergence and Gene Conversion Sculpt PRD Class Repertoires.

The majority of homeobox genes are highly conserved across animals, but the eutherian-specific ETCHbox genes, embryonically expressed and highly divergent duplicates of CRX, are a notable exception. Here we compare the ETCHbox genes of 34 mammalian species, uncovering dynamic patterns of gene loss and tandem duplication, including the presence of a large tandem array of LEUTX loci in the genome of the European rabbit (Oryctolagus cuniculus). Despite extensive gene gain and loss, all sampled species possess at least two ETCHbox genes, suggesting their collective role is indispensable.

The importance of dead material within a tumour on the dynamics in response to radiotherapy.

In vivo tumours are highly heterogeneous, often comprising regions of hypoxia and necrosis. Radiotherapy significantly alters the intratumoural composition. Moreover, radiation-induced cell death may occur via a number of different mechanisms that act over different timescales.

The Evolution of Tumour Composition During Fractionated Radiotherapy: Implications for Outcome.

Current protocols for delivering radiotherapy are based primarily on tumour stage and nodal and metastases status, even though it is well known that tumours and their microenvironments are highly heterogeneous. It is well established that the local oxygen tension plays an important role in radiation-induced cell death, with hypoxic tumour regions responding poorly to irradiation. Therefore, to improve radiation response, it is important to understand more fully the spatiotemporal distribution of oxygen within a growing tumour before and during fractionated radiation.