Homeless youth: Barriers and facilitators for service referrals.

Young people who are homeless and experiencing mental health issues are reluctant to use relevant services for numerous reasons. Youth are also at risk of disengaging from services at times of referral to additional or alternative services. This study aimed to identify barriers and facilitators for inter-service referrals for homeless youth with mental health issues who have already engaged with a service.

EC144 is a potent inhibitor of the heat shock protein 90.

Alkyne 40, 5-(2-amino-4-chloro-7-((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl)-2-methylpent-4-yn-2-ol (EC144), is a second generation inhibitor of heat shock protein 90 (Hsp90) and is substantially more potent in vitro and in vivo than the first generation inhibitor 14 (BIIB021) that completed phase II clinical trials. Alkyne 40 is more potent than 14 in an Hsp90α binding assay (IC(50) = 1.1 vs 5.

Kiwifruit floral gene APETALA2 is alternatively spliced and accumulates in aberrant indeterminate flowers in the absence of miR172.

In Arabidopsis, the identity of perianth and reproductive organs are specified by antagonistic action of two floral homeotic genes, APETALA2 (AP2) and AGAMOUS (AG). AP2 is also negatively regulated by an evolutionary conserved interaction with a microRNA, miR172, and has additional roles in general plant development. A kiwifruit gene with high levels of homology to AP2 and AP2-like genes from other plant species was identified.

Identification and characterization of flowering genes in kiwifruit: sequence conservation and role in kiwifruit flower development.

Background: Flower development in kiwifruit (Actinidia spp.) is initiated in the first growing season, when undifferentiated primordia are established in latent shoot buds. These primordia can differentiate into flowers in the second growing season, after the winter dormancy period and upon accumulation of adequate winter chilling.

Recruitment variability in North Atlantic cod and match-mismatch dynamics.

Background: Fisheries exploitation, habitat destruction, and climate are important drivers of variability in recruitment success. Understanding variability in recruitment can reveal mechanisms behind widespread decline in the abundance of key species in marine and terrestrial ecosystems. For fish populations, the match-mismatch theory hypothesizes that successful recruitment is a function of the timing and duration of larval fish abundance and prey availability.

BIIB021, a synthetic Hsp90 inhibitor, has broad application against tumors with acquired multidrug resistance.

17-AAG, the first-generation clinical Hsp90 inhibitor, exhibits promising antitumor activity in clinical studies, but is limited by poor solubility and hepatotoxicity. To pursue compounds with better biopharmaceutical properties, we have developed a series of fully synthetic orally bioavailable inhibitors of Hsp90. Here, we report that 17-AAG and other ansamycin derivatives are inactive in P-gp and/or MRP-1 expressing cell lines and sensitivity could be restored by coadministration of P-gp or MRP inhibitors.

Rationally designed high-affinity 2-amino-6-halopurine heat shock protein 90 inhibitors that exhibit potent antitumor activity.

Heat shock protein 90 (Hsp90) is a molecular chaperone protein implicated in stabilizing the conformation and maintaining the function of many cell-signaling proteins. Many oncogenic proteins are more dependent on Hsp90 in maintaining their conformation, stability, and maturation than their normal counterparts. Furthermore, recent data show that Hsp90 exists in an activated form in malignant cells but in a latent inactive form in normal tissues, suggesting that inhibitors selective for the activated form could provide a high therapeutic index.

7'-substituted benzothiazolothio- and pyridinothiazolothio-purines as potent heat shock protein 90 inhibitors.

We report on the discovery of benzo- and pyridino- thiazolothiopurines as potent heat shock protein 90 inhibitors. The benzothiazole moiety is exceptionally sensitive to substitutions on the aromatic ring with a 7'-substituent essential for activity. Some of these compounds exhibit low nanomolar inhibition activity in a Her-2 degradation assay (28-150 nM), good aqueous solubility, and oral bioavailability profiles in mice.

Orally active purine-based inhibitors of the heat shock protein 90.

Orally active Hsp90 inhibitors are of interest as potential chemotherapeutic agents. Recently, fully synthetic 8-benzyladenines and 8-sulfanyladenines such as 4 were disclosed as Hsp90 inhibitors, but these compounds are not water soluble and consequently have unacceptably low oral bioavailabilities. We now report that water-solubility can be achieved by inserting an amino functionality in the N(9) side chain.

The topoisomerase II-Hsp90 complex: a new chemotherapeutic target?

The modulation of DNA topology by topoisomerase II plays a crucial role during chromosome condensation and segregation in mitosis and has thus become a highly attractive target for chemotherapeutic drugs. However, these drugs are highly toxic, and so new approaches are required. One such strategy is to target topoisomerase II-interacting proteins.

Synthesis and biological evaluation of a new class of geldanamycin derivatives as potent inhibitors of Hsp90.

The heat shock protein Hsp90 has increasingly become an important therapeutic target especially for treatment of cancers. Inhibition of the ATPase activity of Hsp90 by natural products (e.g.

Safety of esophagoscopy in the irradiated esophagus.

Carcinoma of the esophagus is a disease with a poor prognosis. Surgery is considered the treatment of choice. Patients who are surgically unresectable may receive radiotherapy, plus or minus chemotherapy.

Six month inhalation studies of pirbuterol acetate aerosol in the beagle dog and squirrel monkey.

Groups of Beagle dogs and Squirrel monkeys were exposed to aerosols of pirbuterol acetate, a new bronchodilator at doses of 0, 200, 400 and 800 micrograms of pirbuterol/kg body weight daily for 6 months. Each group consisted of 4 dogs or 6 monkeys per sex. Dogs were exposed by face mask and monkeys were exposed by head only in a manifold.