The role of intestinal immune cells and matrix metalloproteinases in inflammatory bowel disease

Inflammatory bowel disease (IBD) has become globally intractable. MMPs play a key role in many inflammatory diseases. However, little is known about the role of MMPs in IBD. In this study, IBD expression profiles were screened from public Gene Expression Omnibus datasets. Functional enrichment analysis revealed that IBD-related specific functions were associated with immune pathways. Five MMPS-related disease markers, namely MMP-9, CD160, PTGDS, SLC26A8, and TLR5, were selected by machine learning and the correlation between each marker and immune cells was evaluated. We then induced colitis in C57 mice using sodium dextran sulfate and validated model construction through HE staining of the mouse colon. WB and immunofluorescence experiments confirmed that the expression levels of MMP-9, PTGDS, SLC26A8, and CD160 in colitis were significantly increased, whereas that of TLR5 were decreased. Flow cytometry analysis revealed that MMPs regulate intestinal inflammation and immunity mainly through CD8 in colitis. Our findings reveal that MMPs play a crucial role in the pathogenesis of IBD and are related to the infiltration of immune cells, suggesting that MMPs may promote the development of IBD by activating immune infiltration and the immune response. This study provides insights for further studies on the occurrence and development of IBD

7-Ketocholesterol Induces Cell Apoptosis by Activation of Nuclear Factor kappa B in Mouse Macrophages

We investigated the molecular mechanisms responsible for the induction of apoptosis in mouse monocytic macrophage cell line J774A.1 stimulated by 7-ketocholesterol (7-KC). Cell apoptosis was detected by Annexin V-propidium iodide (PI) staining. The DNA-binding activity of nuclear factor kappa B (NF-kappaB) was assessed by electrophoretic mobility shift assay (EMSA). Results showed that 7-KC-stimulation in J774A.1 cells activated NF-kappaB, which is involved in cell apoptosis, in a time- and dose-dependent manners. 7-KC was also found to increase the binding activity of NF-kappaB to specific DNA binding sites, a possible mechanism for the induction of the cell apoptosis. Moreover, these effects were partially inhibited by pyrrolidine dithiocarbamate (PDTC), an NF-kappaB inhibitor. Taken together, 7-KC may be an important factor in atherosclerosis due to the ability of 7-KC to induce cell apoptosis, which is at least partially mediated through the activation of NF-kappaB.</p

Molecular robots guided by prescriptive landscapes

Traditional robots rely for their function on computing, to store internal representations of their goals and environment and to coordinate sensing and any actuation of components required in response. Moving robotics to the single-molecule level is possible in principle, but requires facing the limited ability of individual molecules to store complex information and programs. One strategy to overcome this problem is to use systems that can obtain complex behaviour from the interaction of simple robots with their environment. A first step in this direction was the development of DNA walkers, which have developed from being non-autonomous, to being capable of directed but brief motion on one-dimensional tracks. Here we demonstrate that previously developed random walkers—so-called molecular spiders that comprise a streptavidin molecule as an inert ‘body’ and three deoxyribozymes as catalytic ‘legs’—show elementary robotic behaviour when interacting with a precisely defined environment. Single-molecule microscopy observations confirm that such walkers achieve directional movement by sensing and modifying tracks of substrate molecules laid out on a two-dimensional DNA origami landscape. When using appropriately designed DNA origami, the molecular spiders autonomously carry out sequences of actions such as ‘start’, ‘follow’, ‘turn’ and ‘stop’. We anticipate that this strategy will result in more complex robotic behaviour at the molecular level if additional control mechanisms are incorporated. One example might be interactions between multiple molecular robots leading to collective behaviour; another might be the ability to read and transform secondary cues on the DNA origami landscape as a means of implementing Turing-universal algorithmic behaviour

accelerating vehicle detection in low-altitude airborne urban video

The limitation of the existing methods of traffic data collection is that they rely on techniques that are strictly local in nature. The airborne system in unmanned aircrafts provides the advantages of wider view angle and higher mobility. However, detecting vehicles in airborne videos is a challenging task because of the scene complexity and platform movement. Most of the techniques used in stationary platforms cannot perform well in this situation. A new and efficient method based on Bayes model is proposed in this paper. This method can be divided into two stages, attention focus extraction and vehicle classification. Experimental results demonstrated that, compared with other representative algorithms, our method obtained better performance with higher detection rate, lower false positive rate and faster detection speed. &copy; 2011 IEEE.National Natural Science Foundation of China; Chinese Academy of Science; Microsoft Research Asia; Xian Institute of Optics and Precision Mechanics of CAS; Anhui Crearo Technology Co., LtdThe limitation of the existing methods of traffic data collection is that they rely on techniques that are strictly local in nature. The airborne system in unmanned aircrafts provides the advantages of wider view angle and higher mobility. However, detecting vehicles in airborne videos is a challenging task because of the scene complexity and platform movement. Most of the techniques used in stationary platforms cannot perform well in this situation. A new and efficient method based on Bayes model is proposed in this paper. This method can be divided into two stages, attention focus extraction and vehicle classification. Experimental results demonstrated that, compared with other representative algorithms, our method obtained better performance with higher detection rate, lower false positive rate and faster detection speed. &copy; 2011 IEEE

Analysis of Longitudinal Binomial Data with Positive Association between the Number of Successes and the Number of Failures: An Application to Stock Instability Study

Numerous methods have been developed for longitudinal binomial data in the literature. These traditional methods are reasonable for longitudinal binomial data with a negative association between the number of successes and the number of failures over time; however, a positive association may occur between the number of successes and the number of failures over time in some behaviour, economic, disease aggregation and toxicological studies as the numbers of trials are often random. In this paper, we propose a joint Poisson mixed modelling approach to longitudinal binomial data with a positive association between longitudinal counts of successes and longitudinal counts of failures. This approach can accommodate both a random and zero number of trials. It can also accommodate overdispersion and zero inflation in the number of successes and the number of failures. An optimal estimation method for our model has been developed using the orthodox best linear unbiased predictors. Our approach not only provides robust inference against misspecified random effects distributions, but also consolidates the subject-specific and population-averaged inferences. The usefulness of our approach is illustrated with an analysis of quarterly bivariate count data of stock daily limit-ups and limit-downs

Site-Specific, Covalent Immobilization of Dehalogenase ST2570 Catalyzed by Formylglycine-Generating Enzymes and Its Application in Batch and Semi-Continuous Flow Reactors

Formylglycine-generating enzymes can selectively recognize and oxidize cysteine residues within the sulfatase sub motif at the terminus of proteins to form aldehyde-bearing formylglycine (FGly) residues, and are normally used in protein labeling. In this study, an aldehyde tag was introduced to proteins using formylglycine-generating enzymes encoded by a reconstructed set of the pET28a plasmid system for enzyme immobilization. The haloacid dehalogenase ST2570 from Sulfolobus tokodaii was used as a model enzyme. The C-terminal aldehyde-tagged ST2570 (ST2570CQ) exhibited significant enzymological properties, such as new free aldehyde groups, a high level of protein expression and improved enzyme activity. SBA-15 has widely been used as an immobilization support for its large surface and excellent thermal and chemical stability. It was functionalized with amino groups by aminopropyltriethoxysilane. The C-terminal aldehyde-tagged ST2570 was immobilized to SBA-15 by covalent binding. The site-specific immobilization of ST2570 avoided the chemical denaturation that occurs in general covalent immobilization and resulted in better fastening compared to physical adsorption. The site-specific immobilized ST2570 showed 3-fold higher thermal stability, 1.2-fold higher catalytic ability and improved operational stability than free ST2570. The site-specific immobilized ST2570 retained 60% of its original activity after seven cycles of batch operation, and it was superior to the ST2570 immobilized to SBA-15 by physical adsorption, which loses 40% of its original activity when used for the second time. It is remarkable that the site-specific immobilized ST2570 still retained 100% of its original activity after 10 cycles of reuse in the semi-continuous flow reactor. Overall, these results provide support for the industrial-scale production and application of site-specific, covalently immobilized ST2570

Dynamic Response of Slope Inertia-Based Timoshenko Beam under a Moving Load

In this paper, the dynamic response of a simply supported beam subjected to a moving load is reinvestigated. Based on a new beam theory, slope inertia-based Timoshenko (SIBT), the governing equations of motion of the beam are derived. An analytical solution is presented by using a coupled Fourier and Laplace&ndash;Carson integral transformation method. The finite element solution is also developed and compared with the analytical solution. Then, a comparative study of three beam models based on the SIBT, Euler&ndash;Bernoulli and Timoshenko, subjected to a moving load, is presented. The results show that for slender beams, the dynamic responses calculated by the three theories have marginal differences. However, as the ratio of the cross-sectional size to beam length increases, the dynamic magnification factors for the mid-span displacement obtained by the SIBT and Timoshenko beams become larger than those obtained by the Euler&ndash;Bernoulli beams. Furthermore, until the ratio is greater than 1/3, the difference between the calculated results of the SIBT and Timoshenko beams becomes apparent