Yersinia entomophaga Tc toxin is released by T10SS-dependent lysis of specialized cell subpopulations.

Disease-causing bacteria secrete numerous toxins to invade and subjugate their hosts. Unlike many smaller toxins, the secretion machinery of most large toxins remains enigmatic. By combining genomic editing, proteomic profiling and cryo-electron tomography of the insect pathogen Yersinia entomophaga, we demonstrate that a specialized subset of these cells produces a complex toxin cocktail, including the nearly ribosome-sized Tc toxin YenTc, which is subsequently exported by controlled cell lysis using a transcriptionally coupled, pH-dependent type 10 secretion system (T10SS). Our results dissect the Tc toxin export process by a T10SS, identifying that T10SSs operate via a previously unknown lytic mode of action and establishing them as crucial players in the size-insensitive release of cytoplasmically folded toxins. With T10SSs directly embedded in Tc toxin operons of major pathogens, we anticipate that our findings may model an important aspect of pathogenesis in bacteria with substantial impact on agriculture and healthcare.

Improvement of Whole-body Bone Planar Images on a Bone-dedicated Single-photon Emission Computed Tomography Scanner by Blind Deconvolution Algorithm.

Purpose: We have developed a bone-dedicated collimator with higher sensitivity but slightly degraded resolution on single-photon emission computed tomography (SPECT) for planar bone scintigraphy, compared with conventional low-energy high-resolution collimator. In this work, we investigated the feasibility of using the blind deconvolution algorithm to improve the resolution of planar images on bone scintigraphy. Materials and Methods: Monte Carlo simulation was performed with the NCAT phantom for modeling bone scintigraphy on the clinical dual-head SPECT scanner (Imagine NET 632, Beijing Novel Medical Equipment Ltd.) equipped with the bone-dedicated collimator. Maximum likelihood estimation method was used for the blind deconvolution algorithm. The initial estimation of point spread function (PSF) and iteration number for the method were determined by comparing the deblurred images obtained from different input parameters. We simulated different tumors in five different locations and with five different diameters to evaluate the robustness of the initial inputs. Furthermore, we performed chest phantom studies on the clinical SPECT scanner. The quantified increased contrast ratio (CR) between the tumor and the background was evaluated. Results: The 2 mm PSF kernel and 10 iterations provided a practical and robust deblurred image on our system. Those two inputs can generate robust deblurred images in terms of the tumor location and size with an average increased CR of 21.6%. The phantom studies also demonstrated the ability of blind deconvolution, using those two inputs, with increased CRs of 17%, 17%, 22%, 20%, and 13% for lesions with diameters of 1 cm, 2 cm, 3 cm, 4 cm, and 5 cm, respectively. Conclusions: It is feasible to use the blind deconvolution algorithm to deblur the planar images for SPECT bone scintigraphy. The appropriate values of the PSF kernel and the iteration number for the blind deconvolution can be determined using simulation studies.

Tyrosine hydroxylase inhibits HCC progression by downregulating TGFß/Smad signaling.

The alteration of metabolic processes has been found to have significant impacts on the development of hepatocellular carcinoma (HCC). Nevertheless, the effects of dysfunction of tyrosine metabolism on the development of HCC remains to be discovered. This research demonstrated that tyrosine hydroxylase (TH), which responsible for the initial and limiting step in the bio-generation of the neuro-transmitters dopamine and adrenaline, et al. was shown to be reduced in HCC. Increased expression of TH was found facilitates the survival of HCC patients. In addition, decreased TH indicated larger tumor size, much more numbers of tumor, higher level of AFP, and the presence of cirrhosis. TH effectively impairs the growth and metastasis of HCC cells, a process dependent on the phosphorylation of serine residues (S19/S40). TH directly binds to Smad2 and hinders the cascade activation of TGFß/Smad signaling with the treatment of TGFß1. In summary, our study uncovered the non-metabolic functions of TH in the development of HCC and proposes that TH might be a promising biomarker for diagnosis as well as an innovative target for metastatic HCC.