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BackgroundThe microtubule-associated protein tau accumulates in neurodegenerative diseases known as tauopathies, the most common being Alzheimer's disease. One way to treat these disorders may be to reduce abnormal tau levels through chaperone manipulation, thus subverting synaptic plasticity defects caused by tau's toxic accretion.MethodsTauopathy models were used to study the impact of YM-01 on tau. YM-01 is an allosteric promoter of triage functions of the most abundant variant of the heat shock protein 70 (Hsp70) family in the brain, heat shock cognate 70 protein (Hsc70). The mechanisms by which YM-01 modified Hsc70 activity and tau stability were evaluated with biochemical methods, cell cultures, and primary neuronal cultures from tau transgenic mice. YM-01 was also administered to acute brain slices of tau mice; changes in tau stability and electrophysiological correlates of learning and memory were measured.ResultsTau levels were rapidly and potently reduced in vitro and ex vivo upon treatment with nanomolar concentrations of YM-01. Consistent with Hsc70 having a key role in this process, overexpression of heat shock protein 40 (DNAJB2), an Hsp70 co-chaperone, suppressed YM-01 activity. In contrast to its effects in pathogenic tauopathy models, YM-01 had little activity in ex vivo brain slices from normal, wild-type mice unless microtubules were disrupted, suggesting that Hsc70 acts preferentially on abnormal pools of free tau. Finally, treatment with YM-01 increased long-term potentiation in tau transgenic brain slices.ConclusionsTherapeutics that exploit the ability of chaperones to selectively target abnormal tau can rapidly and potently rescue the synaptic dysfunction that occurs in Alzheimer's disease and other tauopathies.

The Nathanson Creek Parkway and Preserve project spans a 1,000 foot reach of Nathanson Creek, a tributary to Sonoma Creek next to the Sonoma Valley High School grounds (see Appendix A Figures 1-6). The Sonoma Ecology Center (SEC) entered a contract with the city of Sonoma after the creek flooded in 2006 and installed plants between November 2009 and May 2010. The purpose of this project is to analyze plant survivorship data after 1-year of growth and to establish baseline data on the channel morphology for future restoration monitoring. We recorded total plant survivorship, created 5 cross-sectional transects (one every 200ft.), and recorded the plants growing along each transect. We also documented incidents of vandalism and overall site conditions.After one year, the restoration site showed 63.6% survivorship among the flora that were planted plus broadcast seeding of the native grass Blue wildrye (elymus glaucus). This survival rate does not meet the 80% standard set by the SEC for its restoration efforts. Without baseline morphology data, it is too early to come to any conclusions on the relationship between the planting and the channel morphology without, but observations suggest that the re-vegetation has done little to decrease back erosion or mitigate a future flood event.

The chair of the Center to Prevent Handgun Violence explains the center's STAR (Straight Talk about Risks) program, a pre-K-12 curriculum designed to teach children how to reduce their chances of being victimized by gun violence. Students rehearse behaviors that may one day be life saving, such as resisting peer pressure and recognizing and channeling anger in a nonviolent way. (MLH)

A school curriculum program educates children in the US about the dangers of using guns, emphasizing that violence is not the solution for their domestic, academic or social problems, and that the consequences of using guns are very bad. The program advocates counselling of students by their parents and doctors. The program requires new laws that regulate gun sales and ban automatic weapons.