Atomically precise binding conformations of adenine and its variants on gold using single molecule conductance signatures

We demonstrate single molecule conductance as a sensitive and atomically precise probe of binding configurations of adenine and its biologically relevant variants on gold. By combining experimental measurements and density functional theory (DFT) calculations of single molecule–metal junction structures in aqueous conditions, we determine for the first time that robust binding of adenine occurs in neutral or basic pH when the molecule is deprotonated at the imidazole moiety. The molecule binds through the donation of the electron lone pairs from the imidazole nitrogen atoms, N7 and N9, to the gold electrodes. In addition, the pyrimidine ring nitrogen, N3, can bind concurrently and strengthen the overall metal–molecule interaction. The amine does not participate in binding to gold in contrast to most other amine-terminated molecular wires due to the planar geometry of the nucleobase. DFT calculations reveal the importance of interface charge transfer in stabilizing the experimentally observed binding configurations. We demonstrate that biologically relevant variants of adenine, 6-methyladenine and 2′-deoxyadenosine, have distinct conductance signatures. These results lay the foundation for biosensing on gold using single molecule conductance readout.FA9550-19-1-0224 - Department of Defense/AFOSRAccepted manuscrip

The ATP-Dependent Protease ClpP Inhibits Biofilm Formation by Regulating Agr and Cell Wall Hydrolase Sle1 in Staphylococcus aureus

Biofilm causes hospital-associated infections on indwelling medical devices. In Staphylococcus aureus, Biofilm formation is controlled by intricately coordinated network of regulating systems, of which the ATP-dependent protease ClpP shows an inhibitory effect. Here, we demonstrate that the inhibitory effect of ClpP on biofilm formation is through Agr and the cell wall hydrolase Sle1. Biofilm formed by clpP mutant consists of proteins and extracellular DNA (eDNA). The increase of the protein was, at least in part, due to the reduced protease activity of the mutant, which was caused by the decreased activity of agr. On the other hand, the increase of eDNA was due to increased cell lysis caused by the higher level of Sle1. Indeed, as compared with wild type, the clpP mutant excreted an increased level of eDNA, and showed higher sensitivity to Triton-induced autolysis. The deletion of sle1 in the clpP mutant decreased the biofilm formation, the level of eDNA, and the Triton-induced autolysis to wild-type levels. Despite the increased biofilm formation capability, however, the clpP mutant showed significantly reduced virulence in a murine model of subcutaneous foreign body infection, indicating that the increased biofilm formation capability cannot compensate for the intrinsic functions of ClpP during infection

FAST Globular Cluster Pulsar Survey: Twenty-Four Pulsars Discovered in Fifteen Globular Clusters

We present the discovery of 24 pulsars in 15 Globular Clusters (GCs) using the Five-hundred-meter Aperture Spherical radio Telescope (FAST). These include the first pulsar discoveries in M2, M10, and M14. Most of the new systems are either confirmed or likely members of binary systems. M53C, NGC6517H and I are the only three pulsars confirmed to be isolated. M14A is a black widow pulsar with an orbital period of 5.5 hours and a minimum companion mass of 0.016 \Ms. M14E is an eclipsing binary pulsar with an orbital period of 20.3 hours. With the other 8 discoveries that have been reported elsewhere, in total 32 GC pulsars have been discovered by FAST so far. In addition, We detected M3A twice. This was enough to determine that it is a black widow pulsar with an orbital period of 3.3 hours and a minimum companion mass of 0.0125 \Ms.Comment: 12 pages, 2 figures, accepted by ApJL, comments are always welcomed

Critical role of c-Jun overexpression in liver metastasis of human breast cancer xenograft model

<p>Abstract</p> <p>Background</p> <p>c-Jun/AP-1 has been linked to invasive properties of aggressive breast cancer. Recently, it has been reported that overexpression of c-Jun in breast cancer cell line MCF-7 resulted in increased AP-1 activity, motility and invasiveness of the cells <it>in vitro </it>and tumor formation in nude mice. However, the role of c-Jun in metastasis of human breast cancer <it>in vivo </it>is currently unknown.</p> <p>Methods</p> <p>To further investigate the direct involvement of c-Jun in tumorigenesis and metastasis, in the present study, the effects of c-Jun overexpression were studied in both <it>in vitro </it>and in nude mice.</p> <p>Results</p> <p>Ectopic overexpression of c-Jun promoted the growth of MCF-7 cells and resulted in a significant increase in the percentage of cells in S phase and increased motility and invasiveness. Introduction of c-Jun gene alone into weakly invasive MCF-7 cells resulted in the transfected cells capable of metastasizing to the nude mouse liver following tail vein injection.</p> <p>Conclusion</p> <p>The present study confirms that overexpression of c-Jun contributes to a more invasive phenotype in MCF-7 cells. It indicates an interesting relationship between c-Jun expression and increased property of adhesion, migration and <it>in vivo </it>liver metastasis of MCF-7/c-Jun cells. The results provide further evidence that c-Jun is involved in the metastasis of breast cancer. The finding also opens an opportunity for development of anti-c-Jun strategies in breast cancer therapy.</p

Spatial Uncertainty-Aware Semi-Supervised Crowd Counting

Semi-supervised approaches for crowd counting attract attention, as the fully supervised paradigm is expensive and laborious due to its request for a large number of images of dense crowd scenarios and their annotations. This paper proposes a spatial uncertainty-aware semi-supervised approach via regularized surrogate task (binary segmentation) for crowd counting problems. Different from existing semi-supervised learning-based crowd counting methods, to exploit the unlabeled data, our proposed spatial uncertainty-aware teacher-student framework focuses on high confident regions' information while addressing the noisy supervision from the unlabeled data in an end-to-end manner. Specifically, we estimate the spatial uncertainty maps from the teacher model's surrogate task to guide the feature learning of the main task (density regression) and the surrogate task of the student model at the same time. Besides, we introduce a simple yet effective differential transformation layer to enforce the inherent spatial consistency regularization between the main task and the surrogate task in the student model, which helps the surrogate task to yield more reliable predictions and generates high-quality uncertainty maps. Thus, our model can also address the task-level perturbation problems that occur spatial inconsistency between the primary and surrogate tasks in the student model. Experimental results on four challenging crowd counting datasets demonstrate that our method achieves superior performance to the state-of-the-art semi-supervised methods

Qualitative Assessment of Barriers and Facilitators of Access to HIV Testing Among Men Who Have Sex with Men in China

Diagnosis of HIV is the entry point into the continuum of HIV care; a well-recognized necessary condition for the ultimate prevention of onward transmission. In China, HIV testing rates among men who have sex with men (MSM) are low compared to other high risk subgroups, yet experiences with HIV testing among MSM in China are not well understood. To address this gap and prepare for intervention development to promote HIV testing and rapid linkage to treatment, six focus groups (FGs) were conducted with MSM in Beijing (40 HIV-positive MSM participated in one of four FGs and 20 HIV-negative or status unknown MSM participated in one of two FGs). Major themes reported as challenges to HIV testing included stigma and discrimination related to HIV and homosexuality, limited HIV knowledge, inconvenient clinic times, not knowing where to get a free test, fear of positive diagnosis or nosocomial infection, perceived low service quality, and concerns/doubts about HIV services. Key facilitators included compensation, peer support, professionalism, comfortable testing locations, rapid testing, referral and support after diagnosis, heightened sense of risk through engagement in high-risk behaviors, sense of responsibility to protect self, family and partner support, and publicity via social media. Themes and recommendations were generally consistent across HIV-positive and negative/status unknown groups, although examples of enacted stigma were more prevalent in the HIV-positive groups. Findings from our study provide policy suggestions for how to bolster current HIV prevention intervention efforts to enhance ?test-and-treat? strategies for Chinese MSM.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140221/1/apc.2015.0083.pd