The Raf-MEK-ERK1/2 pathway is hyper-activated in a large fraction of colorectal cancers due to mutations in K-Ras and we show that treatment of CRC cell lines with MEK inhibitors causes an increase in Cdx2 expression.
These studies establish germline KRAS mutations as a cause of human disease and infer that the constellation of developmental abnormalities seen in Noonan syndrome spectrum is, in large part, due to hyperactive Ras.
Treatment with Akt inhibitor LY294002 or mTOR inhibitor rapamycin rescued the social deficit, but had no effect on hyperactivity and repetitive behavior/restricted behavior in Cntnap2-/- mice.
Patients with CASPR2 antibodies and an estimated probability of >70% of having anti-CASPR2 encephalitis (n = 22) had limbic encephalitis (n = 18, one patient plus ataxia), Morvan syndrome (n = 2) or a hyperkinetic movement disorder (n = 2).
High-throughput behavioral profiling identifies nighttime hyperactivity in cntnap2 mutants, while pharmacological testing reveals dysregulation of GABAergic and glutamatergic systems.
Cntnap2 homozygous null mice were also hyperactive, froze less during testing, showed a mild gait phenotype and deficits in the three-chamber social preference test, although less robust than previously published.
Cntnap2(-/-) mice show deficits in the three core ASD behavioral domains, as well as hyperactivity and epileptic seizures, as have been reported in humans with CNTNAP2 mutations.
Since hyperactivity of the protein kinase DYRK1A is linked to several neurodegenerative disorders, DYRK1A inhibitors have been suggested as potential therapeutics for Down syndrome and Alzheimer's disease.
DYRK1Ahyperactivity appears to contribute to the development of a number of human malignancies and to cognitive deficits observed in Down syndrome and Alzheimer's disease.
We found that IGFBP6 and SATB2 were significantly down-regulated in HIV-infected CEM*174 cells and 3 different cohorts of HIV/AIDS patients while their promoters were predominantly hyper-methylated compared with normal controls.
The neurobehavioral analysis of these mouse lines showed that DYRK1A overexpressing 152F7 mice but not the other lines display learning impairment and hyperactivity during development.
We found that in Cc2d1a-deficient male mice PDE4D is hyperactive, leading to a reduction in cAMP response element binding protein signaling, but this molecular deficit is not present in female mice.
In alemtuzumab-induced TD, the autoantibodies against the thyrotropin receptor (TRAb) play a major role, and 2 main aspects distinguish this condition from the spontaneous form: (1) up to 20% of GD cases exhibit a fluctuating course, with alternating phases of hyper- and hypothyroidism, due to the coexistence of TRAb with stimulating and blocking function; (2) TRAb are also positive in about 70% of hypothyroid patients, with blocking TRAb responsible for nearly half of the cases.