Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy

Host genetics has an important role in leprosy, and variants in the shared promoter region of PARK2 and PACRG were the first major susceptibility factors identified by positional cloning. Here we report the linkage disequilibrium mapping of the second linkage peak of our previous genome-wide scan, located close to the HLA complex. In both a Vietnamese familial sample and an Indian case-control sample, the low-producing lymphotoxin-alpha (LTA)+80 A allele was significantly associated with an increase in leprosy risk (P = 0.007 and P = 0.01, respectively). Analysis of an additional case-control sample from Brazil and an additional familial sample from Vietnam showed that the LTA+80 effect was much stronger in young individuals. In the combined sample of 298 Vietnamese familial trios, the odds ratio of leprosy for LTA+80 AA/AC versus CC subjects was 2.11 (P = 0.000024), which increased to 5.63 (P = 0.0000004) in the subsample of 121 trios of affected individuals diagnosed before 16 years of age. In addition to identifying LTA as a major gene associated with early-onset leprosy, our study highlights the critical role of case- and population-specific factors in the dissection of susceptibility variants in complex diseases.     

Novel Criteria for Exponential Stability of Linear Non-Autonomous Functional Differential Equations

General linear non-autonomous functional differential equations are considered. Explicit criteria for exponential stability are given. Furthermore, the authors present an explicit robust stability bound for systems subject to time-varying perturbations. Two examples are given to illustrate the obtained results.     

Facile synthesis of FeFe2O4 magnetic nanomaterial for removing methylene blue from aqueous solution

A facile and simple chemical precipitation method was utilized to synthesize FeFe_2O_4 magnetic nanomaterial for removing methylene blue(MB) from aqueous solution. Characterizations of this material were examined by using XRD, SEM, FT-IR, TGA-DTG and BET methods. Factors affecting the uptake of methylene blue, including p H, adsorption time, and MB initial concentration were also studied. The measured data were fitted by using four isotherm models including Langmuir, Freundlich, Sips and Temkin. Results showed that the Sips model offers the best fit to the data. In addition, the monolayer MB adsorption capacity obtained from the Langmuir model was 42.35 mg g~(-1) under the optimal conditions of p H = 10 and adsorption time = 80 min. In particular, the uptake of MB onto FeFe_2O_4 magnetic nanomaterial obtained from the kinetic and mechanism studies of the adsorption was in good agreement with prediction of the pseudo-first-order model, whereas the electrostatic interaction was found to play a primary mechanism.     

Surface PEGylation of hollow mesoporous silica nanoparticles via aminated intermediate

A hybrid of organic/inorganic system, hollow mesoporous silica nanoparticles functionalized with poly(ethylene glycol), was synthesized in the presence of coupling agent and aminated ends. Doxorubicin (DOX) was used as a model drug to evaluate the effect of PEGylation on the loading capacity and release pattern of the system. Characterization with transmission electron microscopy (TEM) and scanning electron microscopy (SEM), X-ray diffraction (XRD), nitrogen adsorption-desorption, thermogravimetric analysis (TGA) and Fourier transformed infrared (FTIR) confirmed the PEG conjugation, as well as the amorphous mesoporous nature of the synthesized particles. Due to the capping effect of PEG molecules over the pores in the silica structure, the synthesized system was able to retain higher amount of cargo and establish a controlled manner when releasing.     

Chromosome 6q25 is linked to susceptibility to leprosy in a Vietnamese population

Leprosy, a chronic infectious disease caused by Mycobacterium leprae, affects an estimated 700,000 persons each year. Clinically, leprosy can be categorized as paucibacillary or multibacillary disease. These clinical forms develop in persons that are intrinsically susceptible to leprosy per se, that is, leprosy independent of its specific clinical manifestation. We report here on a genome-wide search for loci controlling susceptibility to leprosy per se in a panel of 86 families including 205 siblings affected with leprosy from Southern Vietnam. Using model-free linkage analysis, we found significant evidence for a susceptibility gene on chromosome region 6q25 (maximum likelihood binomial (MLB) lod score 4.31; P = 5 x 10(-6)). We confirmed this by family-based association analysis in an independent panel of 208 Vietnamese leprosy simplex families. Of seven microsatellite markers underlying the linkage peak, alleles of two markers (D6S1035 and D6S305) showed strong evidence for association with leprosy (P = 6.7 x 10(-4) and P = 5.9 x 10(-5), respectively).     

Susceptibility to leprosy is associated with PARK2 and PACRG

Leprosy is caused by Mycobacterium leprae and affects about 700,000 individuals each year. It has long been thought that leprosy has a strong genetic component, and recently we mapped a leprosy susceptibility locus to chromosome 6 region q25-q26 (ref. 3). Here we investigate this region further by using a systematic association scan of the chromosomal interval most likely to harbour this leprosy susceptibility locus. In 197 Vietnamese families we found a significant association between leprosy and 17 markers located in a block of approx. 80 kilobases overlapping the 5' regulatory region shared by the Parkinson's disease gene PARK2 and the co-regulated gene PACRG. Possession of as few as two of the 17 risk alleles was highly predictive of leprosy. This was confirmed in a sample of 975 unrelated leprosy cases and controls from Brazil in whom the same alleles were strongly associated with leprosy. Variants in the regulatory region shared by PARK2 and PACRG therefore act as common risk factors for leprosy.     

Progress in electrical energy storage system: A critical review

Electrical energy storage technologies for stationary applications are reviewed.Particular attention is paid to pumped hydroelectric storage,compressed air energy storage,battery,flow battery,fuel cell,solar fuel,superconducting magnetic energy storage, flywheel, capacitor/supercapacitor,and thermal energy torage.Comparison is made among these technologies in terms of technical characteris-tics,applications and deployment status.     

Complex Network Analysis of the Robustness of the Hanoi,Vietnam Bus Network

Many complex networks exist to facilitate the transport of material or information. In this capacity, the authors are often concerned with the continued flow of material or information when a fraction of the links in the complex network is disrupted. In other words, the authors are interested in the robustness of the complex network. In this paper, the authors survey measures of robustness like the average path length, the average clustering coefficient, the global efficiency, the size of largest cluster and use these to analyze the robustness of the bus network in Hanoi, Vietnam. The authors find that the bus network is robust against random failure but sensitive to targeted attack, in agreement with its scale-free character. By examining sharp drops in the average path length within the largest cluster of the Hanoi bus network under successive targeted attack, the authors identify five nodes whose loss lead to the fragmentation of the network into five or six disconnected clusters. These isolated clusters represent geographically the Central, Western, Southern, and Northwestern districts of Hanoi. Special considerations must therefore be given to these five nodes when planners wish to expand the bus network, or make it more robust.     

Modelling schizophrenia using human induced pluripotent stem cells

Schizophrenia (SCZD) is a debilitating neurological disorder with a world-wide prevalence of 1%; there is a strong genetic component, with an estimated heritability of 80-85%. Although post-mortem studies have revealed reduced brain volume, cell size, spine density and abnormal neural distribution in the prefrontal cortex and hippocampus of SCZD brain tissue and neuropharmacological studies have implicated dopaminergic, glutamatergic and GABAergic activity in SCZD, the cell types affected in SCZD and the molecular mechanisms underlying the disease state remain unclear. To elucidate the cellular and molecular defects of SCZD, we directly reprogrammed fibroblasts from SCZD patients into human induced pluripotent stem cells (hiPSCs) and subsequently differentiated these disorder-specific hiPSCs into neurons (Supplementary Fig. 1). SCZD hiPSC neurons showed diminished neuronal connectivity in conjunction with decreased neurite number, PSD95-protein levels and glutamate receptor expression. Gene expression profiles of SCZD hiPSC neurons identified altered expression of many components of the cyclic AMP and WNT signalling pathways. Key cellular and molecular elements of the SCZD phenotype were ameliorated following treatment of SCZD hiPSC neurons with the antipsychotic loxapine. To date, hiPSC neuronal pathology has only been demonstrated in diseases characterized by both the loss of function of a single gene product and rapid disease progression in early childhood. We now report hiPSC neuronal phenotypes and gene expression changes associated with SCZD, a complex genetic psychiatric disorder.