Basic activities of daily living (ADL) are self-maintenance abilities such as dressing or bathing. Instrumental ADL (IADL) are more complex everyday tasks, such as preparing a meal or managing finances (Lawton & Brody, 1969). IADL questionnaires play an important role in assessing the functional abilities of older adults and evaluating the impact of cognitive impairment on routine activities. This paper examined the cognitive processes that underlie IADL performance and concluded that the accurate and reliable execution of IADL likely draws upon the integrity of a wide range of cognitive processes. This review examined IADL in mild cognitive impairment (MCI) because of the controversial nature of distinguishing a significant decline in functional abilities in those with MCI versus dementia or MCI versus cognitively normal aging. The challenges of investigating IADL empirically were explored, as well as some of the reasons for the inconsistent findings in the literature. A review of questionnaire-based assessments of IADL indicated that: MCI can be distinguished statistically from healthy older adults and dementia, individuals with multiple domain MCI are more impaired on IADL than those with single domain MCI, mild IADL changes can be predictive of future cognitive decline, and the ability to manage finances may be among the earliest IADL changes in MCI and a strong predictor of conversion to dementia. This paper concluded with recommendations for more sensitive and reliable IADL questionnaires.

The cerebellum provides an excellent system for understanding how afferent and target neurons coordinate sequential intercellular signals and cell-autonomous genetic programs in development. Mutations in the orphan nuclear receptor RORalpha block Purkinje cell differentiation with a secondary loss of afferent granule cells. We show that early transcriptional targets of RORalpha include both mitogenic signals for afferent progenitors and signal transduction genes required to process their subsequent synaptic input. RORalpha acts through recruitment of gene-specific sets of transcriptional cofactors, including beta-catenin, p300, and Tip60, but appears independent of CBP. One target promoter is Sonic hedgehog, and recombinant Sonic hedgehog restores granule precursor proliferation in RORalpha-deficient cerebellum. Our results suggest a link between RORalpha and beta-catenin pathways, confirm that a nuclear receptor employs distinct coactivator complexes at different target genes, and provide a logic for early RORalpha expression in coordinating expression of genes required for reciprocal signals in cerebellar development.

Malformations affecting the cerebellar vermis are only poorly understood at the genetic level. Dandy-Walker malformations (DWM) are characterized by dilation of the fourth ventricle, anterior rotation of the cerebellum, vermis hypoplasia or agenesis, and hydrocephalus, and they may occur together with other abnormalities (1). Recent work identified a subset of DWM patients carrying interstitial deletions on chromosome 3, most of which were hemizygous for both ZIC1 and ZIC4 (2), transcription factors that promote proliferation of cerebellar granule cell precursors. Mice heterozygous for both Zic1 and Zic4 reproduce several DWM phenotypes, but show more modest effects on other characteristic features (2). Identifying genes with related phenotypes should help to clarify the developmental mechanisms behind such malformations.The nur12 mouse was identified as having an ataxic gait and cerebellar hypoplasia, including agenesis of the vermis, in a large chemical mutagenesis screen (3). Here, we use positional cloning and noncomplementation with a gene trap allele to identify the Ebf-and SMAD-interacting 30 zinc-finger protein, Zfp423 (also known as ROAZ or OAZ) as the gene mutated in nur12 mice. Tsai and Reed (4, 5) first described ROAZ in rat olfactory tissue as an Ebf1 (previously OLF-1, or O/E-1)-interacting protein identified in a yeast two-hybrid assay. Based on the overlapping temporal sequence of Zfp423 and Ebf1 expression in olfactory precursors, they proposed that their interaction maintains olfactory precursors in an immature state, whereas release of Ebf to form homodimers promotes terminal differentiation. Subsequent genetic manipulations indicated that Ebf family members promote neuronal differentiation coupled to cell cycle exit and migration out of germinal zones (6-10). Our results show that Zfp423 is required for proliferation and differentiation by precursor cells in the developing brain. We propose that by forming mutually exclusive complexes with other transcription factors, Zfp423 sharpens the response of precursor cells to external differentiation signals. The phenotypic similarities between nur12 mutant cerebellum and DWM may shed further light on a group of human disorders for which few genetic clues have been found. Results Ataxia and Brain Malformations in nur12Mice. Homozygous nur12 mice have ataxia and tremor [see supporting information (SI) Movie 1] and have a malformation of the cerebellum that is more severe at the vermis than the hemispheres (Fig. 1A) and a pronounced anterior rotation of the cerebellum within the posterior fossa (Fig. 1B). These features are characteristic of certain human hindbrain malformations, including DWM and cerebellar vermis hypoplasia (CVH), but are not common among ataxic mouse mutations. Among intercross progeny, the nur12 cerebellum can range from complete loss of vermis with somewhat smaller hemispheres to almost complete loss of the cerebellum. Within

Using prior research on self and social inference (e.g., S. M. Andersen, 1984) and significant-other representations in social perception (S. M. Andersen & S. W. Cole, 1990), the present study examined a dual-factor conceptualization of self-other differences based on perspective differences and emotional-motivational relevance. Both factors were assumed to contribute to how private versus public aspects of the self, significant others, and nonsignificant others are structured in memory. In an idiographic-nomothetic design, participants' response latencies in completing sentences to characterize private and public aspects of each person were measured, and participants rated how well a pooled, randomized set of these predicates described each aspect of each person. Evidence showed differences in featural richness (availability), distinctiveness, and free-retrieval latency (accessibility) supporting the dual-factor conceptualization of self-other differences.