TRPM3 and miR-204 establish a regulatory circuit that controls oncogenic autophagy in clear cell renal cell carcinoma.

Autophagy promotes tumor growth by generating nutrients from the degradation of intracellular structures. Here we establish, using shRNAs, a dominant-negative mutant, and a pharmacologic inhibitor, mefenamic acid (MFA), that the Transient Receptor Potential Melastatin 3 (TRPM3) channel promotes the growth of clear cell renal cell carcinoma (ccRCC) and stimulates MAP1LC3A (LC3A) and MAP1LC3B (LC3B) autophagy. Increased expression of TRPM3 in RCC leads to Ca(2+) influx, activation of CAMKK2, AMPK, and ULK1, and phagophore formation. In addition, TRPM3 Ca(2+) and Zn(2+) fluxes inhibit miR-214, which directly targets LC3A and LC3B. The von Hippel-Lindau tumor suppressor (VHL) represses TRPM3 directly through miR-204 and indirectly through another miR-204 target, Caveolin 1 (CAV1).

The effects of the environment on autistic spectrum disorder in Jamaica

OBJECTIVE: The prevalence of autistic disorder has been rising worldwide. This disorder is believed to have a genetic basis with an environmental trigger. The clinical presentation has features that are similar to mercury poisoning, suggesting a probable environmental trigger. This paper investigates the relationship between environmental contaminants/toxins, including mercury, and autistic disorder in Jamaica. METHODS: Autistic children were identified from public and private hospital records and from records of special schools. Fifty-eight parents of autistic children completed a questionnaire about their environment and frequency of exposure to harmful chemicals and contaminants during pregnancy and prior to diagnosis. The childhood Autism Rating Scale determined the severity of autistic disorder. The relationship between the severity of autism and different environmental factors was analyzed using the chi-squared test. RESULTS: The meanñStandard Deviation age of autistic children was 6.5ñ3.7 years. There were 79 percent male and 21 percent female. Although there were rates of autism calculated by parish, there are no known apparent links between the geographical region and severity of autism. Sixty percent of the population had changed their address since birth. No association was found between use of common household chemicals (eg bleach, disinfectant), residence close to possible environmental contaminants (eg garbage dumps, factories, bodies of water) and autism, either during pregnancy or prior to diagnosis. A single case of exposure to mercury during pregnancy associated with severe autism was identified. CONCLUSIONS: This study was unable to identify any associations between a number of environmental agents and the severity of autism. The single case of mercury exposure during pregnancy warrants further investigation of this association with a larger sample size (AU)

Depo-provera: a preliminary report on its use on a Family Island in the Commonwealth of the Bahamas

A preliminary report on the use of depo-provera amongst a group of women within childbearing age on an island of the Bahamas shows promise. The duration of administration of the drug in this particular study should be borne in mind when anticipating defaulters (AU)