Here we report the identification of the LIN complex (LINC), a human multiprotein complex that is required for transcriptional activation of G 2 /M genes. LINC is related to the recently identified dREAM and DRM complexes of Drosophila and C. elegans that contain homologs of the mammalian retinoblastoma tumor suppressor protein. The LINC core complex consists of at least five subunits including the chromatin-associated LIN-9 and RbAp48 proteins. LINC dynamically associates with pocket proteins, E2F and B-MYB during the cell cycle. In quiescent cells, LINC binds to p130 and E2F4. During cell cycle entry, E2F4 and p130 dissociate and LINC switches to B-MYB and p107. Chromatin Immunoprecipitation experiments demonstrate that LINC associates with a large number of E2F-regulated promoters in quiescent cells. However, RNAi experiments reveal that LINC is not required for repression. In S-phase, LINC selectively binds to the promoters of G 2 /M genes whose products are required for mitosis and plays an important role in their cell cycle dependent activation.

The present review has been compiled to highlight the role of magnetic resonance imaging (MRI) and MR spectroscopy (MRS) for the investigation of cerebral ischemia in the animal experimental field of basic research. We have focused on stroke investigations analyzing the pathomechanisms of the disease evolution and on new advances in both nuclear MR (NMR) methodology or genetic engineering of transgenic animals for the study of complex molecular relationships and causes of the disease.

Temporary focal ischaemia was induced in wild‐type C57Black/6 mice by thread occlusion of the middle cerebral artery (MCA). Recirculation was started after 60 min and maintained for 24 h, after which the mouse brain was frozen in situ. Development of the cerebral infarct was monitored by diffusion‐, perfusion‐ and T2‐weighted magnetic resonance imaging (MRI) during ischaemia, during the early reperfusion period of 90 min, and at 24 h after reperfusion. Ischaemia caused a marked reduction of the perfusion signal intensity and of the apparent diffusion coefficient (ADC) of tissue water in the ipsilateral MCA territory. In sham‐operated control animals ADC remained unchanged. Hemispheric lesion volume after 1 h MCA occlusion was 53 ± 6% (n = 6), as defined by an ADC decrease of more than 20%. Recirculation reduced hemispheric lesion volume to only 27 ± 13%, while there was a trend towards secondary lesion growth at 24 h. Post‐ischaemic recovery of perfusion was slow, heterogeneous and incomplete. A region‐of‐interest analysis showed only partial and transient recovery of the ADC, particularly in the dorsolateral cortex and lateral caudate putamen, which may be explained by inadequate reperfusion in these regions. Detailed MRI studies of cerebral ischaemia and reperfusion may now also be performed in the transgenic mice. Copyright © 1999 John Wiley & Sons, Ltd.

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