Rac1 controls cell turnover and reversibility of the involution process in postpartum mammary glands.

Cell turnover in adult tissues is essential for maintaining tissue homeostasis over a life span and for inducing the morphological changes associated with the reproductive cycle. However, the underlying mechanisms that coordinate the balance of cell death and proliferation remain unsolved. Using the mammary gland, we have discovered that Rac1 acts as a nexus to control cell turnover. Postlactational tissue regression is characterised by the death of milk secreting alveoli, but the process is reversible within the first 48 h if feeding recommences. In mice lacking epithelial Rac1, alveolar regression was delayed. This defect did not result from failed cell death but rather increased cell turnover. Fitter progenitor cells inappropriately divided, regenerating the alveoli, but cell death also concomitantly accelerated. We discovered that progenitor cell hyperproliferation was linked to nonautonomous effects of Rac1 deletion on the macrophageal niche with heightened inflammation. Moreover, loss of Rac1 impaired cell death with autophagy but switched the cell death route to apoptosis. Finally, mammary gland reversibility failed in the absence of Rac1 as the alveoli failed to recommence lactation upon resuckling.

Eomes function is conserved between zebrafish and mouse and controls left-right organiser progenitor gene expression via interlocking feedforward loops.

The T-box family transcription factor Eomesodermin (Eomes) is present in all vertebrates, with many key roles in the developing mammalian embryo and immune system. Homozygous Eomes mutant mouse embryos exhibit early lethality due to defects in both the embryonic mesendoderm and the extraembryonic trophoblast cell lineage. In contrast, zebrafish lacking the predominant Eomes homologue A (Eomesa) do not suffer complete lethality and can be maintained. This suggests fundamental differences in either the molecular function of Eomes orthologues or the molecular configuration of processes in which they participate. To explore these hypotheses we initially analysed the expression of distinct Eomes isoforms in various mouse cell types. Next we compared the functional capabilities of these murine isoforms to zebrafish Eomesa. These experiments provided no evidence for functional divergence. Next we examined the functions of zebrafish Eomesa and other T-box family members expressed in early development, as well as its paralogue Eomesb. Though Eomes is a member of the Tbr1 subfamily we found evidence for functional redundancy with the Tbx6 subfamily member Tbx16, known to be absent from eutherians. However, Tbx16 does not appear to synergise with Eomesa cofactors Mixl1 and Gata5. Finally, we analysed the ability of Eomesa and other T-box factors to induce zebrafish left-right organiser progenitors (known as dorsal forerunner cells) known to be positively regulated by vgll4l, a gene we had previously shown to be repressed by Eomesa. Here we demonstrate that Eomesa indirectly upregulates vgll4l expression via interlocking feedforward loops, suggesting a role in establishment of left-right asymmetry. Conversely, other T-box factors could not similarly induce left-right organiser progenitors. Overall these findings demonstrate conservation of Eomes molecular function and participation in similar processes, but differential requirements across evolution due to additional co-expressed T-box factors in teleosts, albeit with markedly different molecular capabilities. Our analyses also provide insights into the role of Eomesa in left-right organiser formation in zebrafish.

Investigating the molecular guts of endoderm formation using zebrafish.

The vertebrate endoderm makes major contributions to the respiratory and gastrointestinal tracts and all associated organs. Zebrafish and humans share a high degree of genetic homology and strikingly similar endodermal organ systems. Combined with a multitude of experimental advantages, zebrafish are an attractive model organism to study endoderm development and disease. Recent functional genomics studies have shed considerable light on the gene regulatory programs governing early zebrafish endoderm development, while advances in biological and technological approaches stand to further revolutionize our ability to investigate endoderm formation, function and disease. Here, we discuss the present understanding of endoderm specification in zebrafish compared to other vertebrates, how current and emerging methods will allow refined and enhanced analysis of endoderm formation, and how integration with human data will allow modeling of the link between non-coding sequence variants and human disease.

Quality of root canal treatment performed by undergraduate dental students at the University of Khartoum, Sudan.

The aim of the present study was to evaluate the quality of root canal treatment performed by undergraduate dental students at the University of Khartoum. Assessment was by examination of periapical radiographs of completed endodontically treated teeth, performed by undergraduate dental students. A total of 166 postoperative periapical radiographs compromising 265 roots were included. The quality of endodontic treatment was examined in relation to the length of the root filling in relation to the radiographic apex, the density of the obturation according to presence of voids and the taper of root canal fillings. Adequate length of the root filling was found in 34.7% of the maxillary teeth and in 10.9% of mandibular teeth in this study. Adequate density was found in 38.87% of maxillary and 16.98% of mandibular teeth and appropriate taper was found in 40% of maxillary and 16.6% of mandibular teeth. Overall 24.2% in all evaluated teeth were found to have a root filling of an acceptable quality. This result may be because of insufficient preclinical endodontic training of the students' operators or because of the introduction of students to endodontic clinical practice late in their program.