Temporal Expression of Bacterial Proteins Instructs Host CD4 T Cell Expansion and Th17 Development

Pathogens can substantially alter gene expression within an infected host depending on metabolic or virulence requirements in different tissues, however, the effect of these alterations on host immunity are unclear. Here we visualized multiple CD4 T cell responses to temporally expressed proteins in Salmonella-infected mice. Flagellin-specific CD4 T cells expanded and contracted early, differentiated into Th1 and Th17 lineages, and were enriched in mucosal tissues after oral infection. In contrast, CD4 T cells responding to Salmonella Type-III Secretion System (TTSS) effectors steadily accumulated until bacterial clearance was achieved, primarily differentiated into Th1 cells, and were predominantly detected in systemic tissues. Thus, pathogen regulation of antigen expression plays a major role in orchestrating the expansion, differentiation, and location of antigen-specific CD4 T cells in vivo

Apoptosis resistance downstream of eIF4E: posttranscriptional activation of an anti-apoptotic transcript carrying a consensus hairpin structure

Aberrant activation of the translation initiation machinery is a common property of malignant cells, and is essential for breast carcinoma cells to manifest a malignant phenotype. How does sustained activation of the rate limiting step in protein synthesis so fundamentally alter a cell? In this report, we test the post transcriptional operon theory as a possible mechanism, employing a model system in which apoptosis resistance is conferred on NIH 3T3 cells by ectopic expression of eIF4E. We show (i) there is a set of 255 transcripts that manifest an increase in translational efficiency during eIF4E-mediated escape from apoptosis; (ii) there is a novel prototype 55 nt RNA consensus hairpin structure that is overrepresented in the 5′-untranslated region of translationally activated transcripts; (iii) the identified consensus hairpin structure is sufficient to target a reporter mRNA for translational activation under pro-apoptotic stress, but only when eIF4E is deregulated; and (iv) that osteopontin, one of the translationally activated transcripts harboring the identified consensus hairpin structure functions as one mediator of the apoptosis resistance seen in our model. Our findings offer genome-wide insights into the mechanism of eIF4E-mediated apoptosis resistance and provide a paradigm for the systematic study of posttranscriptional control in normal biology and disease

Fibrotic Myofibroblasts Manifest Genome-Wide Derangements of Translational Control

Background: As a group, fibroproliferative disorders of the lung, liver, kidney, heart, vasculature and integument are common, progressive and refractory to therapy. They can emerge following toxic insults, but are frequently idiopathic. Their enigmatic propensity to resist therapy and progress to organ failure has focused attention on the myofibroblast–the primary effector of the fibroproliferative response. We have recently shown that aberrant beta 1 integrin signaling in fibrotic fibroblasts results in defective PTEN function, unrestrained Akt signaling and subsequent activation of the translation initiation machinery. How this pathological integrin signaling alters the gene expression pathway has not been elucidated. Results: Using a systems approach to study this question in a prototype fibrotic disease, Idiopathic Pulmonary Fibrosis (IPF); here we show organized changes in the gene expression pathway of primary lung myofibroblasts that persist for up to 9 sub-cultivations in vitro. When comparing IPF and control myofibroblasts in a 3-dimensional type I collagen matrix, more genes differed at the level of ribosome recruitment than at the level of transcript abundance, indicating pathological translational control as a major characteristic of IPF myofibroblasts. To determine the effect of matrix state on translational control, myofibroblasts were permitted to contract the matrix. Ribosome recruitment in control myofibroblasts was relatively stable. In contrast, IPF cells manifested large alterations in the ribosome recruitment pattern. Pathological studies suggest an epithelial origin for IPF myofibroblasts through the epithelial to mesenchymal transition (EMT). In accord wit

Catalyst-free direct vapor-phase growth of Zn1−xCuxO micro-cross structures and their optical properties

We report a simple catalyst-free vapor-phase method to fabricate Zn(1−x)Cu(x)O micro-cross structures. Through a series of controlled experiments by changing the location of the substrate and reaction time, we have realized the continuous evolution of product morphology from nanorods into brush-like structures and micro-cross structures at different positions, together with the epitaxial growth of branched nanorods from the central stem with the time extended. The growth mechanism of the Zn(1−x)Cu(x)O micro-cross structures has been proposed to involve the synthesis of Cu/Zn square-like core, surface oxidation, and the secondary growth of nanorod arrays. By the detailed structural analysis of the yielded Zn(1−x)Cu(x)O samples at different locations, we have shown that the CuO phases were gradually formed in Zn(1−x)Cu(x)O, which is significant to induce the usual ZnO hexagonal structures changing into four-folded symmetrical hierarchical micro-cross structures. Furthermore, the visible luminescence can be greatly enhanced by the introduction of Cu, and the observed inhomogeneous cathode luminescence in an individual micro-cross structure is caused by the different distributions of Cu

Regulatory element identification in subsets of transcripts: Comparison and integration of current computational methods

Regulatory elements in mRNA play an often pivotal role in post-transcriptional regulation of gene expression. However, a systematic approach to efficiently identify putative regulatory elements from sets of post-transcriptionally coregulated genes is lacking, hampering studies of coregulation mechanisms. Although there are several analytical methods that can be used to detect conserved mRNA regulatory elements in a set of transcripts, there has been no systematic study of how well any of these methods perform individually or as a group. We therefore compared how well three algorithms, each based on a different principle (enumeration, optimization, or structure/sequence profiles), can identify elements in unaligned untranslated sequence regions. Two algorithms were originally designed to detect transcription factor binding sites, Weeder and BioProspector; and one was designed to detect RNA elements conserved in structure, RNAProfile. Three types of elements were examined: (1) elements conserved in both primary sequence and secondary structure; (2) elements conserved only in primary sequence; and (3) microRNA targets. Our results indicate that all methods can uniquely identify certain known RNA elements, and therefore, integrating the output from all algorithms leads to the most complete identification of elements. We therefore developed an approach to integrate results and guide selection of candidate elements from several algorithms presented as a web service (https://dbw.msi.umn.edu:8443/recit). These findings together with the approach for integration can be used to identify candidate elements from genome-wide post-transcriptional profiling data sets

Perioperative Surgical Home Model Improves Outcomes in Crohn’s Disease Patients Undergoing Disease-Related Surgery

Background. To evaluate Perioperative Surgical Home (PSH) practice model implementation in Crohn’s disease (CD) patients undergoing disease-related surgery. Methods. A retrospective analysis of CD patients requiring disease-related surgery in the Shanghai Ninth People’s Hospital was undertaken. Subjects were divided into a non-PSH group consisting of 49 patients (June 2016 to November 2017) and a PSH group consisting of 72 patients (December 2017 until May 2019). Conventional treatment was used for the non-PSH group, while in the PSH group, a standardized pre- and postoperative management routine was employed. The postoperative lengths of stay and incidences of postoperative complications were analyzed. Results. There were no significant differences in demographics, reasons for surgery, preoperative BMIs, and preoperative hemoglobin between the two groups (P>0.05). The overall incidence of complications in the PSH group was dramatically lower than that in the non-PSH group (26.4% vs. 44.9%, P=0.035). In the PSH group, postoperative length of stay was significantly shorter than that in the non-PSH group (11.5±5.7 vs. 9.0±6.8, P<0.001). Conclusions. The PSH conditioning routine in CD patients undergoing disease-related surgeries suggests a trend of fewer postoperative complications and shorter lengths of hospital stay. The PSH model may have clinical advantages when applied to CD patients

A systematic decision-making method for evaluating design alternatives of product service system based on variable precision rough set

International audienc

Significance of Mannan Binding Lectin-Associated Serine Protease 2 in Urinary Extracellular Vesicles in IgA Nephropathy

Purpose: Immunoglobulin A (IgA) nephropathy (IgAN) is a common chronic glomerulonephritis and the main cause of end-stage renal diseases. Recent evidence suggests that mannan binding lectin associated serine proteases 2 (MASP2) is related to IgAN; therefore, we investigated the expression and significance of MASP2 in serum and urinary extracellular vesicles (UEVs) in patients with IgAN.Methods: Thirty-eight patients with IgAN and 17 healthy controls were enrolled in this study. UEVs were extracted by ultracentrifugation. The separation by ultra-high-speed centrifuge was verified by transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). Candidate internal references (TSG101, CD9, flotillin, β-actin and GAPDH) were identified by western blotting in the control group, and the expression of MASP2 in the UEVs was compared. The levels of MASP2 in the serum and UEVs in the IgAN and control groups were determined by enzyme-linked immunosorbent assay (ELISA).Results: TEM and NTA results demonstrated that UEVs were successfully extracted. Western blotting results confirmed that TSG101 was suitable as an internal reference for this study. Compared with the control group, the IgAN group showed positive expression of MASP2. MASP2 levels in the UEVs, determined by ELISA, showed significant differences between IgAN and control groups, which were significantly positively correlated with the level of urinary microalbumin.Conclusions: The level of MASP2 in UEVs was related to IgAN and shows promise as a biomarker for evaluating the severity of renal injury and prognosis of IgAN, thereby helping to elucidate the role of MASP2 in the mannan-binding lectin pathway