Deformity-causing mechanism of drug Thalidomide discovered

London, Mar 13 (ANI): The primary mechanism by which thalidomide causes malformed limbs in developing embryos has been discovered by scientists at Tokyo Institute of Technology.

The drug’s side-effect gained recognition after many affected children were born to mothers who had been prescribed the drug for morning sickness.

According to research in the journal Science, thalidomide binds to and renders inactive the protein cereblon, which is very important in limb formation.

Drug thalidomide may be effective in the treatment of certain cancers and leprosy, but the fact that it causes birth defects means that for women its use remains risky and controversial.

In the study, the research team, led by Takumi Ito from the Tokyo Institute of Technology in Japan, isolated the negative effects of the “potentially useful” drug.

They set out to discover which target molecules thalidomide bound to in the body. They did this using tiny beads that extracted each individual molecule the drug bound to.

The conclusion was confirmed after the usage of genetic techniques to reduce the production of the cereblon protein in developing zebrafish and chick embryos. The embryos with reduced cereblon had similar developmental defects to those that were treated with thalidomide.

“We [have shown] that cereblon… is a primary target of thalidomide teratogenicity” (or its ability to cause birth defects), the researchers wrote in their Science article.

Dr Ito told BBC News: “Although the mechanism for the teratogenic effect was made clear, the mechanism for its therapeutic effects remains unknown.

“[If we want to develop] a new drug devoid of teratogenic activity, it is important to understand [this] mechanism… this is what we are heading for.” (ANI)

Gene-brain activity pattern combo behind difficult-to-hush babies

Washington, July 14 (ANI): People finding it difficult to soothe their babies need not worry about their parenting skills anymore, for a new study suggests that children’s temperament may be due in part to a combination of a certain gene and a specific pattern of brain activity.

Writing about their findings in the journal Psychological Science, McMaster University researcher Louis Schmidt points out that the pattern of brain activity in the frontal cortex of the brain has been associated with various types of temperament in children.

He highlights the fact that infants who have more activity in the left frontal cortex are characterized as temperamentally “easy” and are easily calmed down, while those with greater activity in the right half of the frontal cortex are temperamentally “negative” and are easily distressed and more difficult to soothe.

In the current study, he and his colleagues focused on the interaction between brain activity and the DRD4 gene to see whether it predicted children’s temperament.

According to background information in the Psychological Science article, previous studies have linked the longer version of this gene to increased sensory responsiveness, risk-seeking behaviour, and attention problems in children.

In the present study, brain activity was measured in 9-month-old infants through electroencephalography (EEG) recordings. When the children were 48 months old, their mothers completed questionnaires regarding their behaviour and DNA samples were taken from the children for analysis of the DRD4 gene.

Schmidt says that the results reveal interesting relations among brain activity, behaviour, and the DRD4 gene.

He says that among the children with more activity in the left frontal cortex at 9 months, those who had the long version of the DRD4 gene were more soothable at 48 months than those who possessed the shorter version of the gene.

However, he adds, the children with the long version of the DRD4 gene, who had more activity in the right frontal cortex, were the least soothable and exhibited more attention problems compared to the other children.

Schmidt says that these findings suggest that the long version of the DRD4 gene may act as a moderator of children’s temperament.

“(The) results suggest that it is possible that the DRD4 long allele plays different roles (for better and for worse) in child temperament (depending on internal conditions or the environment inside their bodies),” note the authors.

They conclude that the pattern of brain activity-that is, greater activation in left or right frontal cortex-may influence whether this gene is a protective factor or a risk factor for soothability and attention problems.

The authors cautioned that there are likely other factors that interact with these two measures in predicting children’s temperament. (ANI)