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Tuberculosis (TB), an infectious bacterial disease caused by Mycobacterium tuberculosis (Mtb), is a major cause of death worldwide. Multidrug‐resistant TB remains a public health crisis and thus novel effective treatments, such as host‐directed therapies (HDTs), are urgently required to overcome the challenges of TB infection. In this study, we evaluated 4 calcium modulators for their effects on Mtb growth in macrophages. Only flunarizine enhanced the bactericidal ability of macrophages against Mtb, which was induced by an increase in phosphorylated calcium/calmodulin (CaM)‐dependent protein kinase II (pCaMKII) levels. We further discovered that the expression of CaM was decreased in Mtb‐infected macrophages and restored following flunarizine treatment; this was associated with phagolysosome maturation and acidification. Consistent with these findings, the anti‐TB ability of macrophages was reduced following the silencing of CaM or inhibition of CAMKII activity. In conclusion, our results demonstrated that flunarizine enhanced the bactericidal ability of macrophages and clarified its CaM–pCAMKII‐dependent mechanism. Therefore, our findings strongly support further studies of this currently approved drug as an HDT candidate for TB therapy. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that transforming growth factor (TGT) β1 plays an immunosuppressive role in clinical tuberculosis. However, the contribution of TGF-β1 gene polymorphisms to human tuberculosis susceptibility remains undetermined. In this study, we showed that single-nucleotide polymorphisms (SNPs) in TGF-β1 gene were associated with increased susceptibility to tuberculosis in the discovery cohort (1533 case patients and 1445 controls) and the validation cohort (832 case patients and 1084 controls), and 2 SNPs located in the promoter region (rs2317130 and rs4803457) are in strong linkage disequilibrium. The SNP rs2317130 was associated with the severity of tuberculosis. Further investigation demonstrated that rs2317130 CC genotype is associated with higher TGF-β1 and interleukin 17A production. The mechanistic study showed that rs2317130 C allele affected TGF-β1 promoter activity by regulating binding activity to nuclear extracts. These findings provide insights into the pathogenic role of TGF-β1 in human tuberculosis and reveal a function for the TGF-β1 promoter SNPs in regulating immune responses during Mycobacterium tuberculosis infection. [ABSTRACT FROM AUTHOR]

This paper proposes a novel multilevel gravity model of migration to study the under-researched topic of urban to urban migration in China. Many previous studies have looked at rural to urban migration in the context of urbanisation and economic development, and at return migration. Very few have looked at what is becoming more important in increasingly urbanised countries, which is the movement from one urban location to another. In the study, we develop a new method that allows for the interconnections between migration flows: between those that share an origin, those that share a destination, and where there is a reciprocal flow between places. A conventional gravity model of migration ignores those connections, risking erroneous estimation of the regression parameters and of their statistical significance. It also ignores that those connections are of substantive interest—they reveal the interconnections between places regarding the numbers of migrants that they send and receive. We motivate and illustrate the advantages of our approach using 2010 interprovincial migration census data for China. The results obtained from the model confirm the effect of distance, of population size and of regional income levels. They show that there is greater variation in the numbers of migrants received by provinces than there is in the numbers sent, and that reciprocal migration between pairs of provinces is an important feature of what is happening in China, especially between the neighbouring provinces of Sichuan and Tibet. [ABSTRACT FROM AUTHOR]

An introduction is presented which discusses articles within the issue on topics including sustainable living in the U.S, cultural change and gender norms.

Background Genetic variation influences susceptibility or resistance to tuberculosis. Interleukin 6 (IL-6) contributes to protection against tuberculosis in mice. However, its role in regulating susceptibility or resistance to tuberculosis in humans is unclear. Methods Genotyping of polymorphisms in IL-6 and IL-6R (CD126) genes was performed in 2 independent cohorts, an experimental population (495 cases and 358 controls) and a validation population (1383 cases and 1149 controls). The associations of the variants with tuberculosis were tested using 2 case-control association studies. In addition, the regulatory effects of single-nucleotide polymorphism rs1800796 (-572C > G) on IL-6 production in plasma and CD14+ monocyte cultures stimulated with a Mycobacterium tuberculosis (M. tuberculosis) product were assessed. Results The rs1800796 polymorphism is associated with increased resistance to tuberculosis (odds ratio [OR], 0.771; 95% confidential interval, .684–.870). The rs1800796GG genotype is strongly associated with reduced risk to tuberculosis (OR, 0.621; 95% CI, .460–.838). Interestingly, CD14+ monocytes isolated from individuals with rs1800796GG genotype produced significantly less IL-6 in response to M. tuberculosis 19-kDa lipoprotein than those with CC or CG genotype. Conclusions We identified a genetic polymorphism in the IL-6 promoter that regulates cytokine production and host resistance to pulmonary tuberculosis in Chinese populations. [ABSTRACT FROM AUTHOR]

In rice (Oryza sativa), brassinosteroids (BRs) induce cell elongation at the adaxial side of the lamina joint to promote leaf bending. We identified a rice mutant (ili1-D) showing an increased lamina inclination phenotype similar to that caused by BR treatment. The ili1-D mutant overexpresses an HLH protein homologous to Arabidopsis thaliana Paclobutrazol Resistance1 (PRE1) and the human Inhibitor of DNA binding proteins. Overexpression and RNA interference suppression of ILI1 increase and reduce, respectively, rice laminar inclination, confirming a positive role of ILI1 in leaf bending. ILI1 and PRE1 interact with basic helix-loop-helix (bHLH) protein IBH1 (ILI1 binding bHLH), whose overexpression causes erect leaf in rice and dwarfism in Arabidopsis. Overexpression of ILI1 or PRE1 increases cell elongation and suppresses dwarf phenotypes caused by overexpression of IBH1 in Arabidopsis. Thus, ILI1 and PRE1 may inactivate inhibitory bHLH transcription factors through heterodimerization. BR increases the RNA levels of ILI1 and PRE1 but represses IBH1 through the transcription factor BZR1. The spatial and temporal expression patterns support roles of ILI1 in laminar joint bending and PRE1/At IBH1 in the transition from growth of young organs to growth arrest. These results demonstrate a conserved mechanism of BR regulation of plant development through a pair of antagonizing HLH/bHLH transcription factors that act downstream of BZR1 in Arabidopsis and rice. [ABSTRACT FROM AUTHOR]