Robert D Jones | PubMed Health

PubMed2006

Comparative proteomic analysis reveals differential expression of Hsp25 following the directed differentiation of mouse embryonic stem cells.

Murine embryonic stem (ES) cells can be committed to neural differentiation with high efficiency in culture through the use of feeder- and serum-free media. This system is proving to be an excellent model to study processes involved in ES cell commitment to neural cell fate. We used this approach to generate neurogenic embryoid bodies (NEBs) in a serum-free culture system to perform proteomic analysis of soluble fractions and identify early changes in protein expression as ES cells differentiate. Ten candidate proteins were altered significantly in expression levels. One of the most significant alterations was for the small heat shock protein Hsp25. Three species of Hsp25 are detected in ES cells, and this expression pattern changes during the first 24 h of differentiation until expression is decreased to levels that are barely detectable at 4 days following differentiation. We used immunofluorescence studies to confirm that following ES cell differentiation, expression of Hsp25 becomes excluded from neural precursors as well as other differentiating cells, making it a potentially useful marker of early ES cell differentiation.

Animals↗

PubMed2006

Knowing "what" and knowing "when".

The ability to situate autobiographical memories accurately in the "time-line" of one's own life is a particular aspect of retrograde memory that has received little attention in well-controlled, systematic studies. Here, we addressed this issue by testing the hypothesis that patients with basal forebrain damage would be impaired in their ability to place various autobiographical memories accurately on a 'time-line' of their life. Seven such subjects were contrasted with 11 medial temporal lobe subjects, 8 brain-damaged comparison subjects, and 18 normal comparison subjects, using a procedure in which subjects placed autobiographical events on a time-line of their life. The basal forebrain group was very impaired in this task, relative to the other groups, and on average, misplaced events by more than five years. Although the basal forebrain group was also impaired in retrieving the contents of autobiographical memory, they did not differ statistically from the medial temporal lobe group in this regard (and the medial temporal lobe group did not have impaired time placement of memories). The results indicate an intriguing dissociation between "knowing what" and "knowing when," and suggest that the basal forebrain contains structures that are especially important for "knowing when." Our findings are compatible with the view that the basal forebrain participates critically in retrieval strategies important for memory chronology, which contrasts with the medial temporal lobe's critical role in relational memory per se.

Adult↗