Tbx1: Transcriptional and Developmental Functions.

Recent data have paved the way to mechanistic studies into the role of Tbx1 during development. Tbx1 is haploinsufficient and is involved in an important genetic disorder. The gene encodes a T-box transcription factor that is expressed from approximately E7.5 in mouse embryos and continues to be expressed in a highly dynamic manner. It is neither a strong transcriptional activator nor a strong repressor, but it regulates a large number of genes through epigenetic modifications. Here, we review recent literature concerning mechanisms of gene regulation by Tbx1 and its role in mammalian development, with a special focus on the cardiac, vascular, and central nervous systems.

Selective overexpression of Comt in prefrontal cortex rescues schizophrenia-like phenotypes in a mouse model of 22q11 deletion syndrome.

The 22q11.2 microdeletion is one of the highest genetic risk factors for schizophrenia. It is not well understood which interactions of deleted genes in 22q11.2 regions are responsible for the pathogenesis of schizophrenia, but catechol-O-methytransferase (COMT) is among the candidates. Df1/+ mice are 22q11.2 deletion syndrome (22q11DS) model mice with a hemizygous deletion of 18 genes in the 22q11-related region. Df1/+ mice showed enhanced response to the dopamine D1 agonist, SKF38393, and the N-methyl-D-aspartate antagonist, MK801, which can be normalized by a GABA(A) receptor agonist, bretazenil, or a GABA(A) α2/α3 receptor agonist, SL651498. Here, we demonstrated the curing effects of virus-mediated reintroduction of Comt to the prefrontal cortex (PFC) in Df1/+ mice. In contrast, both Comt overexpression and Comt inhibition caused an abnormal responsiveness to Bretazenil, a GABA(A) receptor agonist in control mice. Comt overexpression increased MK801-induced interneuronal activation and GABA release in the PFC. The expression levels of GABA-related genes such as Gabrb2 (GABA(A)receptor ß2), Gad2 (glutamic acid decarboxylase 65 (Gad65)) and Reln (Reelin) correlate with a Comt expression level in PFC. Our data suggest that Comt-mediated regulation of GABAergic system might be involved in the behavioral pathogenesis of Df1/+ mice.

Is closure of entire wards necessary to control norovirus outbreaks in hospital? Comparing the effectiveness of two infection control strategies.

The standard approach for norovirus control in hospitals in the UK, as outlined by the Health Protection Agency guidance and implemented previously by Lancashire Teaching Hospitals, involves the early closure of affected wards. However, this has a major impact on bed-days lost and cancelled admissions. In 2008, a new strategy was introduced in the study hospital, key elements of which included closure of affected ward bays (rather than wards), installation of bay doors, enhanced cleaning, a rapid in-house molecular test and an enlarged infection control team. The impact of these changes was assessed by comparing two norovirus seasons (2007-08 and 2009-10) before and after implementation of the new strategy, expressing the contrast between seasons as a ratio (r) of expected counts in the two seasons. There was a significant decrease in the ratio of confirmed hospital outbreaks to community outbreaks (r = 0.317, P = 0.025), the number of days of restricted admissions on hospital wards per outbreak (r = 0.742, P = 0.041), and the number of hospital bed-days lost per outbreak (r = 0.344, P <0.001). However, there was no significant change in the number of patients affected per hospital outbreak (r = 1.080, P = 0.517), or the number of hospital staff affected per outbreak (r = 0.651, P = 0.105). Closure of entire wards during norovirus outbreaks is not always necessary. The changes implemented at the study hospital resulted in a significant reduction in the number of bed-days lost per outbreak, and this, together with a reduction in outbreak frequency, resulted in considerable cost savings.