The activity of the E2F transcription factor is controlled by physical association with the retinoblastoma protein (pRB) and two related proteins, p107 and p130. The pRB family members are thought to control different aspects of E2F activity, but it has been unclear what the respective functions of these proteins might be. To dissect the specific functions of pRB, p107, and p130 we have investigated how the expression of E2F-regulated genes is changed in cultures of primary cells lacking each of these family members. Whereas no changes were found in the expression of E2F-target genes in cells lacking either p107 or p130, deregulated expression of E2F targets was seen in cells lacking pRB and in cells lacking both p107 and p130. Surprisingly, the genes that were disregulated in these two settings were completely different. These findings show that pRB and p107/p130 indeed provide different functions in E2F regulation and identify target genes that are dependent on pRB family proteins for their normal expression.

BackgroundMRI-visible perivascular spaces (PVS) are potential neuroimaging markers of cerebral small vessel disease, but their functional significance and mechanisms remain uncertain. We investigated the association between PVS and cognitive impairment, and other MRI markers of small vessel disease, in a patient cohort of ischaemic stroke/transient ischaemic attack (TIA) referrals.MethodsData were collected from a prospective observational database. Standardised detailed neuropsychological testing was performed. A validated visual rating scale on T2-weighted MRI was used to categorise PVS severity; validated scales were used to assess white matter hyperintensities (WMH), cerebral microbleeds (CMB) and lacunes.ResultsWe included 246 patients (45.1% female, mean age 62 years). No significant association between PVS severity grade in any brain region and impairment in any cognitive domain was identified. In multivariable analysis, WMH and hypertension (but not age) were independently associated with basal ganglia PVS severity (OR: 1.27; p<0.0001 and OR: 4.89; p=0.013, respectively). Increasing PVS severity in the basal ganglia was associated with lacunar stroke subtype (p<0.0001). Age and hypertension (but not WMH or lacunar stroke subtype) were independently associated with centrum semiovale PVS severity (OR: 1.19; p=0.013 and OR: 3.71; p=0.007, respectively).ConclusionsPVS do not have an independent association with cognitive impairment in patients with ischaemic stroke or TIA. The associations with clinical-radiological factors are consistent with the hypothesis that PVS reflect cerebral small vessel disease; the different associations for basal ganglia and centrum semiovale PVS might indicate different underlying small vessel arteriopathies according to PVS anatomical distribution, but this requires further study.

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Apical sublaminar wire and pedicle screw instrumentation both offer similar major curve correction with similar fusion lengths without neurologic problems in the operative treatment of AIS. Although more expensive, pedicle screw constructs had significantly less blood loss and slightly shorter fusion lengths than the sublaminar wire constructs.