Delayed increase in stone tool cutting-edge productivity at the Middle-Upper Paleolithic transition in southern Jordan.

Although the lithic cutting-edge productivity has long been recognized as a quantifiable aspect of prehistoric human technological evolution, there remains uncertainty how the productivity changed during the Middle-to-Upper Paleolithic transition. Here we present the cutting-edge productivity of eight lithic assemblages in the eastern Mediterranean region that represent a chrono-cultural sequence including the Late Middle Paleolithic, Initial Upper Paleolithic, the Early Upper Paleolithic, and the Epipaleolithic. The results show that a major increase in the cutting-edge productivity does not coincide with the conventional Middle-Upper Paleolithic boundary characterized by the increase in blades in the Initial Upper Paleolithic, but it occurs later in association with the development of bladelet technology in the Early Upper Paleolithic. Given increasing discussions on the complexity of Middle-Upper Paleolithic cultural changes, it may be fruitful to have a long-term perspective and employ consistent criteria for diachronic comparisons to make objective assessment of how cultural changes proceeded across conventional chrono-cultural boundaries.

Recovery of the histamine H3 receptor activity lost in yeast cells through error-prone PCR and in vivo selection.

G protein-coupled receptors (GPCRs) are the largest protein family in humans and are important drug targets. Yeast, especially Saccharomyces cerevisiae, is a useful host for modifying the function and stability of GPCRs through protein engineering, which is advantageous for mammalian cells. When GPCRs are expressed in yeast, their function is often impaired. In this study, we performed random mutagenesis using error-prone PCR and then an in vivo screening to obtain mutants that recovered the activity of the human histamine H3 receptor (H3R), which loses its signaling function when expressed in yeast. Four mutations with recovered activity were identified after screening. Three of the mutations were identified near the DRY and NPxxY motifs of H3R, which are important for activation and are commonly found in class A GPCRs. The mutants responded exclusively to the yeast YB1 strain harboring Gi-chimera proteins, showing retention of G protein specificity. Analysis of one of the mutants with recovered activity, C415R, revealed that it maintained its ligand-binding characteristics. The strategy used in this study may enable the recovery of the activity of other GPCRs that do not function in S. cerevisiae and may be useful in creating GPCRs mutants stabilized in their active conformations.

A Case of Tardive Dystonia with Task Specificity Confined to the Lower Extremities only during Walking.

Background: Task-specific dystonia (TSD) confined to the lower extremities (LE) is relatively rare. This report describes dystonia confined to the LE only during forward walking. This case required careful neurological and diagnostic assessment because the patient was taking several neuropsychiatric drugs that cause symptomatic dystonia, such as aripiprazole (ARP). Case: A 53-year-old man visited our university hospital with a complaint of abnormalities in the LE that appeared only during walking. Neurological examinations other than walking were normal. Brain magnetic resonance imaging revealed meningioma in the right sphenoid ridge. The patient had been treated for depression with neuropsychiatric medications for a long time, and his abnormal gait appeared about 2 years after additional administration of ARP. After the meningioma was removed, his symptoms remained. Surface electromyography showed dystonia in both LE during forward walking, although his abnormal gait appeared to be accompanied by spasticity. The patient was tentatively diagnosed with tardive dystonia (TD). Although dystonia did not disappear clinically, it was alleviated after discontinuing ARP. Administration of trihexyphenidyl hydrochloride and concomitant rehabilitation improved his dystonia until return to work, but some residual gait abnormalities remained. Discussion: We report an unusual case of TD with task specificity confined to the LE. The TD was induced by the administration of ARP in combination with multiple psychotropic medications. Careful consideration was required for clinical diagnosis, rehabilitation, and assessment of its relevance to TSD.