Effects of Invariant NKT Cells on Parasite Infections and Hygiene Hypothesis.

Invariant natural killer T (iNKT) cells are unique subset of innate-like T cells recognizing glycolipids. iNKT cells can rapidly produce copious amounts of cytokines upon antigen stimulation and exert potent immunomodulatory activities for a wide variety of immune responses and diseases. We have revealed the regulatory effect of iNKT cells on autoimmunity with a serial of publications. On the other hand, the role of iNKT cells in parasitic infections, especially in recently attractive topic hygiene hypothesis, has not been clearly defined yet. Bacterial and parasitic cell wall is a cellular structure highly enriched in a variety of glycolipids and lipoproteins, some of which may serve as natural ligands of iNKT cells. In this review, we mainly summarized the recent findings on the roles and underlying mechanisms of iNKT cells in parasite infections and their cross-talk with Th1, Th2, Th17, Treg, and innate lymphoid cells. In most cases, iNKT cells exert regulatory or direct cytotoxic roles to protect hosts against parasite infections. We put particular emphasis as well on the identification of the natural ligands from parasites and the involvement of iNKT cells in the hygiene hypothesis

MiR-206-mediated dynamic mechanism of the mammalian circadian clock

<p>Abstract</p> <p>Background</p> <p>As a group of highly conserved small non-coding RNAs with a length of 21~23 nucleotides, microRNAs (miRNAs) regulate the gene expression post-transcriptionally by base pairing with the partial or full complementary sequences in target mRNAs, thus resulting in the repression of mRNA translation and the acceleration of mRNA degradation. Recent work has revealed that miRNAs are essential for the development and functioning of the skeletal muscles where they are. In particular, miR-206 has not only been identified as the only miRNA expressed in skeletal muscles, but also exhibited crucial roles in regulation of the muscle development. Although miRNAs are known to regulate various biological processes ranging from development to cancer, much less is known about their role in the dynamic regulation of the mammalian circadian clock.</p> <p>Results</p> <p>A detailed dynamic model of miR-206-mediated mammalian circadian clock system was developed presently by using Hill-type terms, Michaelis-Menten type and mass action kinetics. Based on a system-theoretic approach, the model accurately predicts both the periodicity and the entrainment of the circadian clock. It also explores the dynamics properties of the oscillations mediated by miR-206 by means of sensitivity analysis and alterations of parameters. Our results show that miR-206 is an important regulator of the circadian clock in skeletal muscle, and thus by study of miR-206 the main features of its mediation on the clock may be captured. Simulations of these processes display that the amplitude and frequency of the oscillation can be significantly altered through the miR-206-mediated control.</p> <p>Conclusions</p> <p>MiR-206 has a profound effect on the dynamic mechanism of the mammalian circadian clock, both by control of the amplitude and control or alteration of the frequency to affect the level of the gene expression and to interfere with the temporal sequence of the gene production or delivery. This undoubtedly uncovers a new mechanism for regulation of the circadian clock at a post-transcriptional level and provides important insights into the normal development as well as the pathological conditions of skeletal muscles, such as the aging, chronic disease and cancer.</p

Magnetoresistance in Thin Permalloy Film (10nm-thick and 30-200nm-wide) Nanocontacts Fabricated by e-Beam Lithography

In this paper we show spin dependent transport experiments in nanoconstrictions ranging from 30 to 200nm. These nanoconstrictions were fabricated combining electron beam lithography and thin film deposition techniques. Two types of geometries have been fabricated and investigated. We compare the experimental results with the theoretical estimation of the electrical resistance. Finally we show that the magnetoresistance for the different geometries does not scale with the resistance of the structure and obtain drops in voltage of 20mV at 20Oe.Comment: 15 pages, 4 figures. Accepted by AP

An Equivalent Model of Gas Networks for Dynamic Analysis of Gas-Electricity Systems

The increasing coupling between natural gas and electricity systems by gas-fired generation units brings new challenges to system analysis, such as pressure variations due to consumption perturbations of generation units. The emerging issues require revolutionary modeling and analysis techniques. This paper proposes a novel model to quantify gas pressure variations due to gas-fired power unit ramping and the impact of constraints from natural gas pressure change on ramp rates of gas-fired plants. By utilizing Laplace transform to resolve the governing equations of gas networks, the proposed model can significantly reduce modeling complexity and computational burden. The dynamic behaviors in time scale in s-domain and spatial partial differential equations are transformed into finite difference equations. By introducing the concept of transfer matrices, the relation between states at each node of gas systems can be expressed by transfer parameter matrices. Additionally, a simplified model is introduced to simply the analysis. The explicit expressions of nodal pressure variations in response to demand change are very convenient for analyzing system dynamic performance under disturbances, identifying the most influential factors. The new models are extensively demonstrated on three natural gas networks and benchmarked with traditional simulation approaches. Results illustrate that they produce very close results with the simulation approach, particularly when gas pipelines are long and enter steady states.</p

A Novel Method of Polynomial Approximation for Parametric Problems in Power Systems

Many problems in power systems depend on parameters, which could be stochastic variables or deterministic system control variables practically, e.g., generation outputs, nodal voltages, etc. Due to the nonlinearity of power systems, the analytical relation between system states and parameters cannot be obtained directly. Using the sampling method to evaluate the influence of parameters on system states is very powerful but time-consuming. One feasible approach is to use polynomial approximations, where the system states are approximately expressed in the form of polynomials in terms of parameters. Galerkin method can be used to identify the approximate solution with high accuracy by solving high-dimensional equations. However, if a large number of parameters are involved, solving these high-dimensional equations becomes a serious challenge. This paper proposes an innovative method for resolving these high-dimensional equations in power systems, which constructs a sequence of decoupled equations to determine the polynomial expansion coefficients. This new approach can provide a local approximation in the form of Taylor expansion at a given operation point. Although the method is general, for simplicity and good readability, we introduce the detailed process in its application to load flow problems. Case studies from 6-, 118-, and 1648-bus system show that the proposed method provides approximation more efficiently than traditional Galerkin method does, and 3-order polynomials can give very accurate results.</p

Effects of Invariant NKT Cells on Parasite Infections and Hygiene Hypothesis

Invariant natural killer T (iNKT) cells are unique subset of innate-like T cells recognizing glycolipids. iNKT cells can rapidly produce copious amounts of cytokines upon antigen stimulation and exert potent immunomodulatory activities for a wide variety of immune responses and diseases. We have revealed the regulatory effect of iNKT cells on autoimmunity with a serial of publications. On the other hand, the role of iNKT cells in parasitic infections, especially in recently attractive topic &quot;hygiene hypothesis,&quot; has not been clearly defined yet. Bacterial and parasitic cell wall is a cellular structure highly enriched in a variety of glycolipids and lipoproteins, some of which may serve as natural ligands of iNKT cells. In this review, we mainly summarized the recent findings on the roles and underlying mechanisms of iNKT cells in parasite infections and their cross-talk with Th1, Th2, Th17, Treg, and innate lymphoid cells. In most cases, iNKT cells exert regulatory or direct cytotoxic roles to protect hosts against parasite infections. We put particular emphasis as well on the identification of the natural ligands from parasites and the involvement of iNKT cells in the hygiene hypothesis

A Systematic Prediction of Multiple Drug-Target Interactions from Chemical, Genomic, and Pharmacological Data

In silico prediction of drug-target interactions from heterogeneous biological data can advance our system-level search for drug molecules and therapeutic targets, which efforts have not yet reached full fruition. In this work, we report a systematic approach that efficiently integrates the chemical, genomic, and pharmacological information for drug targeting and discovery on a large scale, based on two powerful methods of Random Forest (RF) and Support Vector Machine (SVM). The performance of the derived models was evaluated and verified with internally five-fold cross-validation and four external independent validations. The optimal models show impressive performance of prediction for drug-target interactions, with a concordance of 82.83%, a sensitivity of 81.33%, and a specificity of 93.62%, respectively. The consistence of the performances of the RF and SVM models demonstrates the reliability and robustness of the obtained models. In addition, the validated models were employed to systematically predict known/unknown drugs and targets involving the enzymes, ion channels, GPCRs, and nuclear receptors, which can be further mapped to functional ontologies such as target-disease associations and target-target interaction networks. This approach is expected to help fill the existing gap between chemical genomics and network pharmacology and thus accelerate the drug discovery processes

Metformin ameliorates ionizing irradiation-induced long-term hematopoietic stem cell injury in mice

AbstractExposure to ionizing radiation (IR) increases the production of reactive oxygen species (ROS) not only by the radiolysis of water but also through IR-induced perturbation of the cellular metabolism and disturbance of the balance of reduction/oxidation reactions. Our recent studies showed that the increased production of intracellular ROS induced by IR contributes to IR-induced late effects, particularly in the hematopoietic system, because inhibition of ROS production with an antioxidant after IR exposure can mitigate IR-induced long-term bone marrow (BM) injury. Metformin is a widely used drug for the treatment of type 2 diabetes. Metformin also has the ability to regulate cellular metabolism and ROS production by activating AMP-activated protein kinase. Therefore, we examined whether metformin can ameliorate IR-induced long-term BM injury in a total-body irradiation (TBI) mouse model. Our results showed that the administration of metformin significantly attenuated TBI-induced increases in ROS production and DNA damage and upregulation of NADPH oxidase 4 expression in BM hematopoietic stem cells (HSCs). These changes were associated with a significant increase in BM HSC frequency, a considerable improvement in in vitro and in vivo HSC function, and complete inhibition of upregulation of p16Ink4a in HSCs after TBI. These findings demonstrate that metformin can attenuate TBI-induced long-term BM injury at least in part by inhibiting the induction of chronic oxidative stress in HSCs and HSC senescence. Therefore, metformin has the potential to be used as a novel radioprotectant to ameliorate TBI-induced long-term BM injury

milR4 and milR16 Mediated Fruiting Body Development in the Medicinal Fungus Cordyceps militaris

Cordyceps militaris readily performs sexual reproduction, thus providing a remarkably rich model for understanding the processes involved in sexual development. It could regulate expression of human genes by diet-derived miRNA-like RNAs (milRNAs). However, the study of miRNAs in C. militaris has been limited. In the present study, genes encoding Dicers, Argonautes, and RNA-dependent RNA polymerases were identified. Illumina deep sequencing was performed to characterize the milRNAs in C. militaris at asexual and sexual development stages. Total 38 milRNAs were identified and five milRNAs were validated by northern blot and qRT-PCR, out of which, 19 were specific for sexual development. Importantly, the fungi could not form fruiting bodies after disruption of milR4, while the perithecium was formed in advance after over-expression of milR4. Abnormal pale yellow fruiting body primordium, covered with abnormal primordium, was formed in the strain with miR16 disruption. Although no milR4 or milR16 target genes were identified, differential expression of many different genes involved in mycelium growth and sexual development (mating process, mating signaling, and fruiting body development) among these mutants were found. Overall, milRNAs play vital roles in sexual development in C. militaris