Lincomycin A is a clinically important antimicrobial agent produced by Streptomyces lincolnensis. In this study, a new regulator designated LmbU (GenBank accession no. ABX00623.1) was identified and characterized to regulate lincomycin biosynthesis in S. lincolnensis wild-type strain NRRL 2936. Both inactivation and overexpression of lmbU resulted in significant influences on lincomycin production. Transcriptional analysis and in vivo neomycin resistance (Neo r ) reporter assays demonstrated that LmbU activates expression of the lmbA, lmbC, lmbJ, and lmbW genes and represses expression of the lmbK and lmbU genes. Electrophoretic mobility shift assays (EMSAs) demonstrated that LmbU can bind to the regions upstream of the lmbA and lmbW genes through the consensus and palindromic sequence 5=-CGCCG GCG-3=. However, LmbU cannot bind to the regions upstream of the lmbC, lmbJ, lmbK, and lmbU genes as they lack this motif. These data indicate a complex transcriptional regulatory mechanism of LmbU. LmbU homologues are present in the biosynthetic gene clusters of secondary metabolites of many other actinomycetes. Furthermore, the LmbU homologue from Saccharopolyspora erythraea (GenBank accession no. WP_009944629.1) also binds to the regions upstream of lmbA and lmbW, which suggests widespread activity for this regulator. LmbU homologues have no significant structural similarities to other known cluster-situated regulators (CSRs), which indicates that they belong to a new family of regulatory proteins. In conclusion, the present report identifies LmbU as a novel transcriptional regulator and provides new insights into regulation of lincomycin biosynthesis in S. lincolnensis. IMPORTANCE Although lincomycin biosynthesis has been extensively studied, its regulatory mechanism remains elusive. Here, a novel regulator, LmbU, which regulates transcription of its target genes in the lincomycin biosynthetic gene cluster (lmb gene cluster) and therefore promotes lincomycin biosynthesis, was identified in S. lincolnensis strain NRRL 2936. Importantly, we show that this new regulatory element is relatively widespread across diverse actinomycetes species. In addition, our findings provide a new strategy for improvement of yield of lincomycin through manipulation of LmbU, and this approach could also be evaluated in other secondary metabolite gene clusters containing this regulatory protein.

Motivated by the occurrence of superconductivity transition in Cu-doped topological insulator Bi 2 Se 3 , we perform a combined study of low temperature scanning tunneling microscopy/spectroscopy and angle-resolved photoemission spectroscopy experiments and of ab initio density functional theory to clarify the doping nature of Cu atoms in Bi 2 Se 3 films. By measuring the structural and electronic properties of the Cu-doped Bi 2 Se 3 films at different doping temperatures, we find that Cu atoms behave as donors at intercalated and interstitial sites in Bi 2 Se 3 films. Only the interstitial defect density plays an important role in the observation of Landau quantization of the topological surface states in Bi 2 Se 3 .

Objectives To examine the relationship between lexical tone perception and melodic pitch perception in Mandarin-speaking cochlear implant (CI) users, and to investigate the influence of previous acoustic hearing on CI users’ speech and music perception. Design Lexical tone perception and melodic contour identification (MCI) were measured in 21 prelingual and 11 postlingual young (age: 6–26 years old) Mandarin-speaking CI users. Lexical tone recognition was measured for four tonal patterns: Tone 1 (flat F0), Tone 2 (rising F0), Tone 3 (falling-rising F0), and Tone 4 (falling F0). MCI was measured using 9 five-note melodic patterns that contained changes in pitch contour, as well as different semitone spacing between notes. Results Lexical tone recognition was generally good (overall mean = 81% correct), and there was no significant difference between subject groups. MCI performance was generally poor (mean = 23% correct). MCI performance was significantly better for postlingual (mean = 32% correct) than for prelingual CI participants (18% correct). After correcting for outliers, there was no significant correlation between lexical tone recognition and MCI performance for prelingual or post-lingual CI participants. Age at deafness was significantly correlated with MCI performance only for postlingual participants. CI experience was significantly correlated with MCI performance for both prelingual and postlingual participants. Duration of deafness was significantly correlated with tone recognition only for prelingual participants. Conclusions Despite the prevalence of pitch cues in Mandarin, the present CI participants had great difficulty perceiving melodic pitch. The availability of amplitude and duration cues in lexical tones most likely compensated for the poor pitch perception observed with these CI listeners. Previous acoustic hearing experience seemed to benefit postlingual CI users’ melodic pitch perception. Longer CI experience was associated with better MCI performance for both subject groups, suggesting that CI users’ music perception may improve as they gain experience with their device.