A Paired Phase and Magnitude Reconstruction for Advanced Diffusion-Weighted Imaging.

OBJECTIVE: Multi-shot interleaved echo planer imaging (Ms-iEPI) can obtain diffusion-weighted images (DWI) with high spatial resolution and low distortion, but suffers from ghost artifacts introduced by phase variations between shots. In this work, we aim at solving the ms-iEPI DWI reconstructions under inter-shot motions and ultra-high b-values. METHODS: An iteratively joint estimation model with paired phase and magnitude priors is proposed to regularize the reconstruction (PAIR). The former prior is low-rankness in the k-space domain. The latter explores similar edges among multi-b-value and multi-direction DWI with weighted total variation in the image domain. The weighted total variation transfers edge information from the high SNR images (b-value = 0) to DWI reconstructions, achieving simultaneously noise suppression and image edges preservation. RESULTS: Results on simulated and in vivo data show that PAIR can remove inter-shot motion artifacts very well (8 shots) and suppress the noise under the ultra-high b-value (4000 s/mm2) significantly. CONCLUSION: The joint estimation model PAIR with complementary priors has a good performance on challenging reconstructions under inter-shot motions and a low signal-to-noise ratio. SIGNIFICANCE: PAIR has potential in advanced clinical DWI applications and microstructure research.

The impact of cell structure, metabolism and group behavior for the survival of bacteria under stress conditions.

Microbes from diverse types of habitats are continuously exposed to external challenges, which may include acidic, alkaline, and toxic metabolites stress as well as nutrient deficiencies. To promote their own survival, bacteria have to rapidly adapt to external perturbations by inducing particular stress responses that typically involve genetic and/or cellular changes. In addition, pathogenic bacteria need to sense and withstand these environmental stresses within a host to establish and maintain infection. These responses can be, in principle, induced by changes in bacterial cell structure, metabolism and group behavior. Bacterial nucleic acids may serve as the core part of the stress response, and the cell envelope and ribosomes protect genetic structures from damage. Cellular metabolism and group behavior, such as quorum sensing system, can play a more important role in resisting stress than we have now found. Since bacteria survival can be only appreciated if we better understand the mechanisms behind bacterial stress response, here we review how morphological and physiological features may lead to bacterial resistance upon exposure to particular stress-inducing factors.

A multivalent vaccine candidate targeting enterotoxigenic Escherichia coli fimbriae for broadly protecting against porcine post-weaning diarrhea.

Fimbriae-mediated initial adherence is the initial and critical step required for enterotoxigenic Escherichia coli (ETEC) infection. Therefore, vaccine candidates have been developed that target these fimbriae and induce specific anti-fimbriae antibodies to block initial ETEC attachment. While this vaccine effectively protects against ETEC-associated post-weaning diarrhea (PWD), developing a broadly effective vaccine against initial ETEC attachment remains a challenging problem, owing to the immunological heterogeneity among these antigens. Here, we applied multi-epitope fusion antigen (MEFA) technology to construct a FaeG-FedF-FanC-FasA-Fim41a MEFA using the adhesive subunits of predominant fimbriae K88 and F18 as the backbone, which also integrated epitopes from adhesive subunits of the rare fimbriae K99, 987P, and F41; we then generated a MEFA computational model and tested the immunogenicity of this MEFA protein in immunized mice. We next evaluated the potential of the fimbriae-targeted MEFA as a vaccine candidate to effectively prevent PWD using in vitro assessment of its anti-fimbriae, antibody-directed inhibition of bacterial adherence. Computational modeling showed that all relevant epitopes were exposed on the MEFA surface and mice subcutaneously immunized with the MEFA protein developed IgG antibodies to all five fimbriae. Moreover, anti-fimbriae antibodies induced by the MEFA protein significantly inhibited the adhesion of K88+, F18+, K99+, 987P+, and F41+ ETEC strains to piglet small intestinal IPEC-1 and IPEC-J2 cell lines. Taken together, these results indicate that FaeG-FedF-FanC-FasA-Fim41a MEFA protein induced specific anti-fimbriae neutralizing antibodies against the five targeted fimbriae. Critically, these results show the potential of fimbriae-targeted MEFA and indicate their promise as a broad, effective vaccine against PWD.

The role of bacterial cell envelope structures in acid stress resistance in E. coli.

Acid resistance (AR) is an indispensable mechanism for the survival of neutralophilic bacteria, such as Escherichia coli (E. coli) strains that survive in the gastrointestinal tract. E. coli acid tolerance has been extensively studied during past decades, with most studies focused on gene regulation and mechanisms. However, the role of cell membrane structure in the context of acid stress resistance has not been discussed in depth. Here, we provide a comprehensive review of the roles and mechanisms of the E. coli cell envelope from different membrane components, such as membrane proteins, fatty acids, chaperones, and proton-consuming systems, and particularly focus on the innovative effects revealed by recent studies. We hope that the information guides us to understand the bacterial survival strategies under acid stress and to further explore the AR regulatory mechanisms to prevent or treat E. coli and other related Gram-negative bacteria infection, or to enhance the AR of engineering E. coli.

Engineered Recombinant Escherichia coli Probiotic Strains Integrated with F4 and F18 Fimbriae Cluster Genes in the Chromosome and Their Assessment of Immunogenic Efficacy in Vivo.

F4 (K88) and F18 fimbriaed enterotoxigenic Escherichia coli (ETEC) are the predominant causes of porcine postweaning diarrhea (PWD), and vaccines are considered the most effective preventive approach against PWD. Since heterologous DNA integrated into bacterial chromosomes could be effectively expressed with stable inheritance, we chose probiotic EcNc (E. coli Nissle 1917 prototype cured of cryptic plasmids) as a delivery vector to express the heterologous F4 or both F4 and F18 fimbriae and sequentially assessed their immune efficacy of anti-F4 and F18 fimbriae in both murine and piglet models. Employing the CRISPR-cas9 technology, yjcS, pcadA, lacZ, yieN/trkD, maeB, and nth/tppB sites in the chromosome of an EcNc strain were targeted as integration sites to integrate F4 or F18 fimbriae cluster genes under the Ptet promotor to construct two recombinant integration probiotic strains (RIPSs), i.e., nth integration strain (EcNcΔnth/tppB::PtetF4) and multiple integration strain (EcNc::PtetF18x4::PtetF4x2). Expression of F4, both F4 and F18 fimbriae on the surfaces of two RIPSs, was verified with combined methods of agglutination assay, Western blot, and immunofluorescence microscopy. The recombinant strains have improved adherence to porcine intestinal epithelial cell lines. Mice and piglets immunized with the nth integration strain and multiple integration strain through gavage developed anti-F4 and both anti-F4 and anti-F18 IgG immune responses. Moreover, the serum antibodies from the immunized mice and piglets significantly inhibited the adherence of F4+ or both F4+ and F18+ ETEC wild-type strains to porcine intestinal cell lines in vitro, indicating the potential of RIPSs as promising probiotic strains plus vaccine candidates against F4+/F18+ ETEC infection.

Targeting ideal oral vaccine vectors based on probiotics: a systematical view.

Probiotics have great potential to be engineered into oral vaccine delivery systems, which can facilitate elicitation of mucosal immunity without latent risks of pathogenicity. Combined with the progressive understanding of probiotics and the mucosal immune system as well as the advanced biotechniques of genetic engineering, the development of promising oral vaccine vectors based on probiotics is available while complicated and demanding. Therefore, a systematical view on the design of practical probiotic vectors is necessary, which will help to logically analyze and resolve the problems that might be neglected during our exploration. Here, we attempt to systematically summarize several fundamental issues vital to the effectiveness of the vector of probiotics, including the stability of the engineered vectors, the optimization of antigen expression, the improvement of colonization, and the enhancement of immunoreactivity. We also compared the existent strategies and some developing ones, attempting to figure out an optimal strategy that might deserve to be referred in the future development of oral vaccine vectors based on probiotics.

Lorentzian sparsity based spectroscopic reconstruction for fast high-dimensional magnetic resonance spectroscopy.

Two-dimensional magnetic resonance spectroscopy (2D MRS) is challenging, even with state-of-art compressive sensing methods, such as L1-sparsity method. In this work, using the prior that the 2D MRS can be regarded as a series of Lorentzian functions, we aim to develop a robust Lorentzian-sparsity based spectroscopy reconstruction method for high-dimensional MRS. The proposed method sparsifies 2D MRS in Lorentzian functions. Instead of thousands of pixel-wise variables, this Lorentzian-sparsity method significantly reduces the number of unknowns to several geometric variables, such as the center, magnitude and shape parameters for each Lorentzian function. The spectroscopy reconstruction is formulated as a nonlinear and nonconvex optimization problem, and the simulated annealing algorithm is developed to solve the problem. The proposed method was compared with inverse FFT method and L1-sparsity method, under various undersampling factors. While FFT and L1 results contained severe artifacts, the Lorentzian-sparsity results provided significantly improved spectroscopy. A new 2D MRS reconstruction method is proposed using the Lorentzian sparsity, with significantly improved MRS reconstruction quality, in comparison with standard inverse FFT method or state-of-art L1-sparsity method.