A Computational Framework for Heparan Sulfate Sequencing Using High-resolution Tandem Mass Spectra

Heparan sulfate (HS) is a linear polysaccharide expressed on cell surfaces, in extracellular matrices and cellular granules in metazoan cells. Through non-covalent binding to growth factors, morphogens, chemokines, and other protein families, HS is involved in all multicellular physiological activities. Its biological activities depend on the fine structures of its protein-binding domains, the determination of which remains a daunting task. Methods have advanced to the point that mass spectra with information-rich product ions may be produced on purified HS saccharides. However, the interpretation of these complex product ion patterns has emerged as the bottleneck to the dissemination of these HS sequencing methods. To solve this problem, we designed HS-SEQ, the first comprehensive algorithm for HS de novo sequencing using high-resolution tandem mass spectra. We tested HS-SEQ using negative electron transfer dissociation (NETD) tandem mass spectra generated from a set of pure synthetic saccharide standards with diverse sulfation patterns. The results showed that HS-SEQ rapidly and accurately determined the correct HS structures from large candidate pools

Liver-heart crosstalk controls IL-22 activity in cardiac protection after myocardial infarction.

Interleukin (IL)-22 regulates tissue inflammation and repair. Here we report participation of the liver in IL-22-mediated cardiac repair after acute myocardial infarction (MI). Methods: We induced experimental MI in mice by ligation of the left ascending artery and evaluated the effect of IL-22 on post-MI cardiac function and ventricular remodeling. Results: Daily subcutaneous injection of 100 µg/kg mouse recombinant IL-22 for seven days attenuated adverse ventricular remodeling and improved cardiac function in mice at 28 days after left anterior descending coronary artery ligation-induced MI. Pharmacological inhibition of signal transducer and activator of transcription (STAT3) muted these IL-22 activities. While cardiomyocyte-selective depletion of STAT3 did not affect IL-22 activities in protecting post-MI cardiac injury, hepatocyte-specific depletion of STAT3 fully muted these IL-22 cardioprotective activities. Hepatocyte-derived fibroblast growth factor (FGF21) was markedly increased in a STAT3-dependent manner following IL-22 administration and accounted for the cardioprotective benefit of IL-22. Microarray analyses revealed that FGF21 controlled the expression of cardiomyocyte genes that are involved in cholesterol homeostasis, DNA repair, peroxisome, oxidative phosphorylation, glycolysis, apoptosis, and steroid responses, all of which are responsible for cardiomyocyte survival. Conclusions: Supplementation of IL-22 in the first week after acute MI effectively prevented left ventricular dysfunction and heart failure. This activity of IL-22 involved crosstalk between the liver and heart after demonstrating a role of the hepatic STAT3-FGF21 axis in IL-22-induced post-MI cardiac protection

Relationships between athletic ability and academic performance in primary school students: A 3-year follow-up study

BackgroundThe aim of this study was to examine whether academic performance is associated with students' athletic ability in primary school.MethodsA 3-year follow-up study was conducted among 1,136 Chinese students. Sit-up and jump rope testers were used to measure 1-min sit-ups and 1-min jump ropes, respectively. Meanwhile, the Pittsburgh Sleep Quality Scale and the Beck Depression Inventory were used to estimate sleep quality and depression levels. The end-of-semester examinations were used to evaluate students' academic performance during the follow-up period.ResultsAfter adjusting for confounders, the mean change in Chinese language performance for participants stratified by 1-min sit-ups at baseline was 0.35 (95% CI: −0.37 to 0.76) for level 1 (slowest), 0.52 (95% CI: −0.54 to 1.08) for level 2, and 1.72 (95% CI: 1.14 to 2.30) for level 3 (fastest) (P for trend = 0.003); the mean change in math scores was 0.28 (95% CI: −0.50 to 0.95) for level 1 (slowest), 0.95 (95% CI: 0.38 to 1.52) for level 2, and 1.41 (95% CI: 0.82 to 1.99) for level 3 (fastest) (P for trend = 0.048). The mean change in foreign language scores was −0.45 (95% CI: −0.99 to −0.93) for level 1 (slowest), −0.14 (95% CI: −0.44 to 0.41) for level 2, and 0.69 (95% CI: 0.25 to 1.13) for level 3 (fastest) (P for trend = 0.004). The mean change in Chinese language performance for participants stratified by 1-min jump ropes at the baseline was 0.30 (95% CI: −0.16 to 0.76) for level 1 (slowest), 1.09 (95% CI: 0.42 to 1.76) for level 2, and 1.74 (95% CI: 1.14 to 2.35) for level 3 (fastest) (P for trend = 0.001). The mean change in math scores was 0.41 (95% CI: −0.11 to 0.92) for level 1 (slowest), 1.44 (95% CI: 0.69 to 2.19) for level 2, and 1.43 (95% CI: 0.76 to 2.10) for level 3 (fastest) (P for trend = 0.019). The mean change in foreign language performance was −0.71 (95% CI: −1.08 to −0.33) for level 1 (slowest), 0.95 (95% CI: −0.40 to 1.50) for level 2, and 0.91 (95% CI: 0.41 to 1.41) for level 3 (fastest) (P for trend < 0.001).ConclusionThis study suggests that participation in jump rope and sit-up exercises may positively affect students' academic performance

Genomewide association study of leprosy.

BACKGROUND: The narrow host range of Mycobacterium leprae and the fact that it is refractory to growth in culture has limited research on and the biologic understanding of leprosy. Host genetic factors are thought to influence susceptibility to infection as well as disease progression. METHODS: We performed a two-stage genomewide association study by genotyping 706 patients and 1225 controls using the Human610-Quad BeadChip (Illumina). We then tested three independent replication sets for an association between the presence of leprosy and 93 single-nucleotide polymorphisms (SNPs) that were most strongly associated with the disease in the genomewide association study. Together, these replication sets comprised 3254 patients and 5955 controls. We also carried out tests of heterogeneity of the associations (or lack thereof) between these 93 SNPs and disease, stratified according to clinical subtype (multibacillary vs. paucibacillary). RESULTS: We observed a significant association (P<1.00x10(-10)) between SNPs in the genes CCDC122, C13orf31, NOD2, TNFSF15, HLA-DR, and RIPK2 and a trend toward an association (P=5.10x10(-5)) with a SNP in LRRK2. The associations between the SNPs in C13orf31, LRRK2, NOD2, and RIPK2 and multibacillary leprosy were stronger than the associations between these SNPs and paucibacillary leprosy. CONCLUSIONS: Variants of genes in the NOD2-mediated signaling pathway (which regulates the innate immune response) are associated with susceptibility to infection with M. leprae

Synthesis and applications of porous non-silica metal oxide submicrospheres

© 2016 Royal Society of Chemistry. Nowadays the development of submicroscale products of specific size and morphology that feature a high surface area to volume ratio, well-developed and accessible porosity for adsorbates and reactants, and are non-toxic, biocompatible, thermally stable and suitable as synergetic supports for precious metal catalysts is of great importance for many advanced applications. Complex porous non-silica metal oxide submicrospheres constitute an important class of materials that fulfill all these qualities and in addition, they are relatively easy to synthesize. This review presents a comprehensive appraisal of the methods used for the synthesis of a wide range of porous non-silica metal oxide particles of spherical morphology such as porous solid spheres, core-shell and yolk-shell particles as well as single-shell and multi-shell particles. In particular, hydrothermal and low temperature solution precipitation methods, which both include various structure developing strategies such as hard templating, soft templating, hydrolysis, or those taking advantage of Ostwald ripening and the Kirkendall effect, are reviewed. In addition, a critical assessment of the effects of different experimental parameters such as reaction time, reaction temperature, calcination, pH and the type of reactants and solvents on the structure of the final products is presented. Finally, the practical usefulness of complex porous non-silica metal oxide submicrospheres in sensing, catalysis, biomedical, environmental and energy-related applications is presented

Graphene-Based Nanocomposites for Energy Storage

Since the first report of using micromechanical cleavage method to produce graphene sheets in 2004, graphene/graphene-based nanocomposites have attracted wide attention both for fundamental aspects as well as applications in advanced energy storage and conversion systems. In comparison to other materials, graphene-based nanostructured materials have unique 2D structure, high electronic mobility, exceptional electronic and thermal conductivities, excellent optical transmittance, good mechanical strength, and ultrahigh surface area. Therefore, they are considered as attractive materials for hydrogen (H2) storage and high-performance electrochemical energy storage devices, such as supercapacitors, rechargeable lithium (Li)-ion batteries, Li–sulfur batteries, Li–air batteries, sodium (Na)-ion batteries, Na–air batteries, zinc (Zn)–air batteries, and vanadium redox flow batteries (VRFB), etc., as they can improve the efficiency, capacity, gravimetric energy/power densities, and cycle life of these energy storage devices. In this article, recent progress reported on the synthesis and fabrication of graphene nanocomposite materials for applications in these aforementioned various energy storage systems is reviewed. Importantly, the prospects and future challenges in both scalable manufacturing and more energy storage-related applications are discussed

Real-time Monitoring for the Next Core-Collapse Supernova in JUNO

Core-collapse supernova (CCSN) is one of the most energetic astrophysical events in the Universe. The early and prompt detection of neutrinos before (pre-SN) and during the SN burst is a unique opportunity to realize the multi-messenger observation of the CCSN events. In this work, we describe the monitoring concept and present the sensitivity of the system to the pre-SN and SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is a 20 kton liquid scintillator detector under construction in South China. The real-time monitoring system is designed with both the prompt monitors on the electronic board and online monitors at the data acquisition stage, in order to ensure both the alert speed and alert coverage of progenitor stars. By assuming a false alert rate of 1 per year, this monitoring system can be sensitive to the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos up to about 370 (360) kpc for a progenitor mass of 30$M_{\odot}$ for the case of normal (inverted) mass ordering. The pointing ability of the CCSN is evaluated by using the accumulated event anisotropy of the inverse beta decay interactions from pre-SN or SN neutrinos, which, along with the early alert, can play important roles for the followup multi-messenger observations of the next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure