Relationships between age, fMRI correlates of familiarity and familiarity-based memory performance under single and dual task conditions.

Using fMRI, we investigated the effects of age and divided attention on the neural correlates of familiarity and their relationship with memory performance. At study, word pairs were visually presented to young and older participants under the requirement to make a relational judgment on each pair. Participants were then scanned while undertaking an associative recognition test under single and dual (auditory tone detection) task conditions.

Relationships between age, fMRI correlates of familiarity and familiarity-based memory performance under single and dual task conditions.

Using fMRI, we investigated the effects of age and divided attention on the neural correlates of familiarity and their relationship with memory performance. At study, word pairs were visually presented to young and older participants under the requirement to make a relational judgment on each pair. Participants were then scanned while undertaking an associative recognition test under single and dual (auditory tone detection) task conditions.

Transcranial magnetic stimulation of right dorsolateral prefrontal cortex does not affect associative retrieval in healthy young or older adults.

We examined whether post-retrieval monitoring processes supporting memory performance are more resource limited in older adults than younger individuals. We predicted that older adults would be more susceptible to an experimental manipulation that reduced the neurocognitive resources available to support post-retrieval monitoring. Young and older adults received transcranial magnetic stimulation (TMS) to the right dorsolateral prefrontal cortex (DLPFC) or a vertex control site during an associative recognition task.

Divided attention at retrieval does not influence neural correlates of recollection in young or older adults.

Age-related decline in episodic memory has been partially attributed to older adults' reduced domain general processing resources. In the present study, we examined the effects of divided attention (DA) - a manipulation assumed to further deplete the already limited processing resources of older adults - on the neural correlates of recollection in young and older adults. Participants underwent fMRI scanning while they performed an associative recognition test in single and dual (tone detection) task conditions.

Neural correlates of post-retrieval monitoring in older adults are preserved under divided attention, but are decoupled from memory performance.

Post-retrieval monitoring is associated with engagement of anterior cingulate and dorsolateral prefrontal cortex. Recent fMRI studies reported age-invariant monitoring effects in these regions and an age-invariant correlation between these effects and memory performance. The present study examined monitoring effects during associative recognition (difference in activity elicited by 'rearranged' and 'intact' test pairs) under single and dual (tone detection) task conditions in young and older adults (Ns = 28 per group).

Age differences in the neural correlates of the specificity of recollection: An event-related potential study.

In young adults, the neural correlates of successful recollection vary with the specificity (or amount) of information retrieved. We examined whether the neural correlates of recollection are modulated in a similar fashion in older adults. We compared event-related potential (ERP) correlates of recollection in samples of healthy young and older adults (N = 20 per age group).

Age-related Differences in Prestimulus Subsequent Memory Effects Assessed with Event-related Potentials.

Prestimulus subsequent memory effects (preSMEs)-differences in neural activity elicited by a task cue at encoding that are predictive of later memory performance-are thought to reflect differential engagement of preparatory processes that benefit episodic memory encoding. We investigated age differences in preSMEs indexed by differences in ERP amplitude just before the onset of a study item. Young and older adults incidentally encoded words for a subsequent memory test.

A Read-Aloud Storybook Selection System for Prereaders at the Preschool Language Level: A Pilot Study.

Purpose: Many well-accepted systems for determining difficulty level exist for books children read independently, but few are available for determining the wide range of difficulty levels of storybooks read aloud to preschoolers. Also, the available tools list book characteristics only on the basis of parents' or authors' opinions. We created an empirically derived difficulty-level system on the basis of 22 speech-language pathologists' (SLPs) judgments of specific storybooks used in preschooler read-alouds.

The Hsp40 J-domain stimulates Hsp70 when tethered by the client to the ATPase domain.

The Escherichia coli Hsp40 DnaJ uses its J-domain (Jd) to couple ATP hydrolysis and client protein capture in Hsp70 DnaK. Fusion of the Jd to peptide p5 (as in Jdp5) dramatically increases the apparent affinity of the p5 moiety for DnaK in the presence of ATP, and Jdp5 stimulates ATP hydrolysis in DnaK by several orders of magnitude. NMR experiments with [(15)N]Jdp5 demonstrated that the peptide tethers the Jd to the ATPase domain.

LINE-1 methylation in plasma DNA as a biomarker of activity of DNA methylation inhibitors in patients with solid tumors.

Multiple clinical trials are investigating the use of the DNA methylation inhibitors azacitidine and decitabine for the treatment of solid tumors. Clinical trials in hematological malignancies have shown that optimal activity does not occur at their maximum tolerated doses but selection of an optimal biological dose and schedule for use in solid tumor patients is hampered by the difficulty of obtaining tumor tissue to measure their activity. Here we investigate the feasibility of using plasma DNA to measure the demethylating activity of the DNA methylation inhibitors in patients with solid tumors.

Neoadjuvant platelet derived growth factor receptor inhibitor therapy combined with docetaxel and androgen ablation for high risk localized prostate cancer.

Purpose: Platelet derived growth factor receptor inhibitor therapy improves the efficacy of taxane chemotherapy in preclinical models of prostate cancer. Men with high risk localized prostate cancer were treated with platelet derived growth factor receptor inhibitor therapy, docetaxel and hormone ablation in the preoperative setting, and clinicopathological outcomes were evaluated.

Materials And Methods: A total of 36 men with cT2 or greater disease, Gleason grade 8-10, serum prostate specific antigen more than 20 ng/ml or cT2b and prostate specific antigen more than 10 ng/ml and Gleason 7 disease, without radiological evidence of metastases, were scheduled to receive intramuscular leuprolide, 600 mg daily oral imatinib and 30 mg/m(2) weekly docetaxel x 4 every 42 days for 3 cycles before radical prostatectomy (beta [0.

The role of the DIF motif of the DnaJ (Hsp40) co-chaperone in the regulation of the DnaK (Hsp70) chaperone cycle.

To perform effectively as a molecular chaperone, DnaK (Hsp70) necessitates the assistance of its DnaJ (Hsp40) co-chaperone partner, which efficiently stimulates its intrinsically weak ATPase activity and facilitates its interaction with polypeptide substrates. In this study, we address the function of the conserved glycine- and phenylalanine-rich (G/F-rich) region of the Escherichia coli DnaJ in the DnaK chaperone cycle. We show that the G/F-rich region is critical for DnaJ co-chaperone functions in vivo and that despite a significant degree of sequence conservation among the G/F-rich regions of Hsp40 homologs from bacteria, yeast, or humans, functional complementation in the context of the E.

The J-domain of Hsp40 couples ATP hydrolysis to substrate capture in Hsp70.

The Escherichia coli Hsp40 DnaJ uses its J-domain to target substrate polypeptides for binding to the Hsp70 DnaK, but the mechanism of J-domain function has been obscured by a substrate-like interaction between DnaJ and DnaK. ATP hydrolysis in DnaK is associated with a conformational change that captures the substrate, and both DnaJ and substrate can stimulate ATP hydrolysis. However, substrates cannot trigger capture by DnaK in the presence of ATP, and substrates stimulate a DnaK conformational change that is uncoupled from ATP hydrolysis.