No abstract

To explore the changes of brain structure and function in attention-deficit/hyperactivity disorder (ADHD), fifteen ADHD patients (inattention subtype) and 15 normal control participants were recruited, the brain structure and function of these subjects were investigated by combining structural magnetic resonance imaging (MRI), diffusion tensor imaging and resting-state functional MRI. The results showed that ADHD patients had a significant decrease in the volume of the white matter (P = 0.04), and a trend toward decreased volume of brain structures except for the putamen and globus pallidus. The visualization of statistical difference maps of the cortical thickness showed that ADHD patients had focal thinning in bilateral frontal regions and the right cingulate cortex (P < 0.05 uncorrected, except for a cluster threshold of 10 voxels). Statistical analysis of the FA maps revealed that ADHD patients had significantly decreased FA in the forceps minor, the internal capsule, the corona radiata, the splenium of the corpus callosum, and the bilateral basal ganglia (P < 0.05 uncorrected as above). ADHD patients had significantly decreased functional connectivity in the anterior cingulate cortex, posterior cingulate cortex, lateral prefrontal cortex, left precuneus and thalamus, but increased functional connectivity in bilateral posterior medial frontal cortex in the default mode network (P < 0.05 uncorrected as above). Our results provide new insights into the changes of the brain structure and function in ADHD, which suggests that alterations in the brain structural and functional connectivity might implicate the pathophysiology of ADHD.

Eukaryotic initiation factor 4A (eIF4A) is an RNA-dependent ATPase and ATP-dependent RNA helicase that is thought to melt the 5 proximal secondary structure of eukaryotic mRNAs to facilitate attachment of the 40S ribosomal subunit. eIF4A functions in a complex termed eIF4F with two other initiation factors (eIF4E and eIF4G). Two isoforms of eIF4A, eIF4AI and eIF4AII, which are encoded by two different genes, are functionally indistinguishable. A third member of the eIF4A family, eIF4AIII, whose human homolog exhibits 65% amino acid identity to human eIF4AI, has also been cloned from Xenopus and tobacco, but its function in translation has not been characterized. In this study, human eIF4AIII was characterized biochemically. While eIF4AIII, like eIF4AI, exhibits RNA-dependent ATPase activity and ATP-dependent RNA helicase activity, it fails to substitute for eIF4AI in an in vitro-reconstituted 40S ribosome binding assay. Instead, eIF4AIII inhibits translation in a reticulocyte lysate system. In addition, whereas eIF4AI binds independently to the middle and carboxy-terminal fragments of eIF4G, eIF4AIII binds to the middle fragment only. These functional differences between eIF4AI and eIF4AIII suggest that eIF4AIII might play an inhibitory role in translation under physiological conditions. All cellular (except organellar) eukaryotic mRNAs possess a cap structure, m 7 GpppN (where N is any nucleotide), at the 5Ј terminus. The interaction of the cap structure with the eukaryotic initiation factor 4F (eIF4F) is important for efficient translation of the mRNA. eIF4F, in association with the RNA binding protein eIF4B, is thought to unwind the secondary structure in the 5Ј untranslated region of an mRNA to facilitate the binding of the 40S ribosome preinitiation complex (for reviews, see references 29, 35, and 52

In conclusion, the efficacy of immunotherapy is dependent on the metastatic location. Treatment appears more active in lymph nodes compared to other organ sites such as liver, adrenals and bone. Future strategies may include additional local treatment in case of oligoprogression in these organs in patients with otherwise sustained treatment benefit.