DMPFinder - Finding differentiating pathways with gaps from two groups of metabolic networks

Session 2B: Biological and Regulatory NetworksWhy some strains of a species exhibit a certain phenotype (e.g. drug resistant) but not the other strains of the same species is a critical question to answer. Studying the metabolism of the two groups of strains may discover the corresponding pathways that are conserved in the first group but not in the second group. However, only a few tools provide functions to compare two groups of metabolic networks which are usually limited to the reaction level, not the pathway level. In this paper, we formulate the DMP (Differentiating Metabolic Pathway) problem for finding conserved pathways exist in first group, but not the second group. The problem also captures the mutation in pathways and derives a measure (p-value and e-score) for evaluating the confident of the pathways. We then developed an algorithm, DMPFinder, to solve the DMP problem. Experimental results show that DMPFinder is able to identify pathways that are critical for the first group to exhibit a certain phenotype which is absent in the other group. Some of these pathways cannot be identified by other tools which only consider reaction level or do not take into account possible mutations among species. The software is available at: http://i.cs.hku.hk/alse/hkubrg/projects/DMPFinder/postprintThe 3rd International Conference on Bioinformatics and Computational Biology (BICoB 2011), New Orleans, LA., 23-25 March 2011

Electrospray deposition and direct patterning of polylactic acid nanofibrous microcapsules for tissue engineering

Electrospun nanofibers composed of biodegradable polymers are attractive candidates for cell culture scaffolds in tissue engineering. Their fine-meshed structures, resembling natural extracellular matrices, effectively interact with cell surfaces and promote cell proliferation. The application of electrospinning, however, is limited to two-dimensional (2D) or single tube-like scaffolds, and the fabrication of arbitrary three-dimensional (3D) scaffolds from electrospun nanofibers is still very difficult due to the fibers’ continuous and entangled form. To address this issue, in this paper, we describe the use of phase-separation-assisted electrospray and electrostatic focusing to perform continuous direct 3D patterning of nanofibrous microcapsules of biodegradable polylactic acid (PLA). These microcapsules exhibit fiber-particle duality because they are composed of nanofibers suitable for cell attachment while also being easy to handle as particles for direct 3D patterning. By varying the flow rate of the polymer solution and the humidity of the electrospray atmosphere during electrospraying, the diameter of the microcapsule and its surface porosity can be controlled. The utility of the direct-patterning process is demonstrated by fabricating high-aspect-ratio microscaffolds and subsequent cell cultures. The nanofibrous and hollow structure of the microcapsules combined with the direct 3D patterning process offers a new approach for fabricating tailor-made scaffolds for regenerative medicine

The GB Virus C (GBV-C) NS3 Serine Protease Inhibits HIV-1 Replication in a CD4+ T Lymphocyte Cell Line without Decreasing HIV Receptor Expression

Introduction: Persistent infection with GBV-C (GB Virus C), a non-pathogenic virus related to hepatitis C virus (HCV), prolongs survival in HIV infection. Two GBV-C proteins, NS5A and E2, have been shown previously to inhibit HIV replication in vitro. We investigated whether the GBV-C NS3 serine protease affects HIV replication. Results: GBV-C NS3 protease expressed in a human CD4+ T lymphocyte cell line significantly inhibited HIV replication. Addition of NS4A or NS4A/4B coding sequence to GBV-C NS3 increased the effect on HIV replication. Inhibition of HI

Nel positively regulates the genesis of retinal ganglion cells by promoting their differentiation and survival during development

Peer reviewedPublisher PD

Forming a three-dimensional porous organic network via solid-state explosion of organic single crystals

Solid-state reaction of organic molecules holds a considerable advantage over liquid-phase processes in the manufacturing industry. However, the research progress in exploring this benefit is largely staggering, which leaves few liquid-phase systems to work with. Here, we show a synthetic protocol for the formation of a three-dimensional porous organic network via solid-state explosion of organic single crystals. The explosive reaction is realized by the Bergman reaction (cycloaromatization) of three enediyne groups on 2,3,6,7,14,15-hexaethynyl-9,10-dihydro-9,10-[1,2]benzenoanthracene. The origin of the explosion is systematically studied using single-crystal X-ray diffraction and differential scanning calorimetry, along with high-speed camera and density functional theory calculations. The results suggest that the solid-state explosion is triggered by an abrupt change in lattice energy induced by release of primer molecules in the 2,3,6,7,14,15-hexaethynyl-9,10-dihydro-9,10-[1,2]benzenoanthracene crystal lattice

Novel Vaccines to Human Rabies

Rabies, the most fatal of all infectious diseases, remains a major public health problem in developing countries, claiming the lives of an estimated 55,000 people each year. Most fatal rabies cases, with more than half of them in children, result from dog bites and occur among low-income families in Southeast Asia and Africa. Safe and efficacious vaccines are available to prevent rabies. However, they have to be given repeatedly, three times for pre-exposure vaccination and four to five times for post-exposure prophylaxis (PEP). In cases of severe exposure, a regimen of vaccine combined with a rabies immunoglobulin (RIG) preparation is required. The high incidence of fatal rabies is linked to a lack of knowledge on the appropriate treatment of bite wounds, lack of access to costly PEP, and failure to follow up with repeat immunizations. New, more immunogenic but less costly rabies virus vaccines are needed to reduce the toll of rabies on human lives. A preventative vaccine used for the immunization of children, especially those in high incidence countries, would be expected to lower fatality rates. Such a vaccine would have to be inexpensive, safe, and provide sustained protection, preferably after a single dose. Novel regimens are also needed for PEP to reduce the need for the already scarce and costly RIG and to reduce the number of vaccine doses to one or two. In this review, the pipeline of new rabies vaccines that are in pre-clinical testing is provided and an opinion on those that might be best suited as potential replacements for the currently used vaccines is offered

OntoFox: web-based support for ontology reuse

<p>Abstract</p> <p>Background</p> <p>Ontology development is a rapidly growing area of research, especially in the life sciences domain. To promote collaboration and interoperability between different projects, the OBO Foundry principles require that these ontologies be open and non-redundant, avoiding duplication of terms through the re-use of existing resources. As current options to do so present various difficulties, a new approach, MIREOT, allows specifying import of single terms. Initial implementations allow for controlled import of selected annotations and certain classes of related terms.</p> <p>Findings</p> <p>OntoFox <url>http://ontofox.hegroup.org/</url> is a web-based system that allows users to input terms, fetch selected properties, annotations, and certain classes of related terms from the source ontologies and save the results using the RDF/XML serialization of the Web Ontology Language (OWL). Compared to an initial implementation of MIREOT, OntoFox allows additional and more easily configurable options for selecting and rewriting annotation properties, and for inclusion of all or a computed subset of terms between low and top level terms. Additional methods for including related classes include a SPARQL-based ontology term retrieval algorithm that extracts terms related to a given set of signature terms and an option to extract the hierarchy rooted at a specified ontology term. OntoFox's output can be directly imported into a developer's ontology. OntoFox currently supports term retrieval from a selection of 15 ontologies accessible via SPARQL endpoints and allows users to extend this by specifying additional endpoints. An OntoFox application in the development of the Vaccine Ontology (VO) is demonstrated.</p> <p>Conclusions</p> <p>OntoFox provides a timely publicly available service, providing different options for users to collect terms from external ontologies, making them available for reuse by import into client OWL ontologies.</p

Polymorphisms in the SAA1/2 Gene Are Associated with Carotid Intima Media Thickness in Healthy Han Chinese Subjects: The Cardiovascular Risk Survey

BACKGROUND: Serum amyloid A protein (SAA) is not only an inflammatory factor, but also an apolipoprotein that can replace apolipoprotein A1 (apoA1) as the major apolipoprotein of high-density lipoprotein (HDL), which has been linked to atherosclerosis. However, the relationship between genetic polymorphisms of SAA and the intima-media thickness (IMT) of the common carotid artery in healthy subjects remains unclear. We investigated the role of SAA1 and SAA2 gene polymorphisms with IMT in a cohort of healthy subjects participating in the Cardiovascular Risk Survey (CRS) study. METHODOLOGY/PRINCIPAL FINDINGS: Anthropometric and B-mode ultrasound of the carotid IMT were measured in 1914 subjects (849 men; 1065 women) recruited from seven cities in Xinjiang province, (western China). Four SNPs (rs12218, rs2229338, rs1059559, and rs2468844) were genotyped by use of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The SNP rs12218 was associated with carotid IMT by analyses of a dominate model (P<0.001) and additive model (P = 0.003), and the difference remained significant after multivariate adjustment (P = 0.008, P<0.001, respectively). This relationship was also observed in rs2468844 after multivariate adjustment by recessive model analysis (P = 0.011) but this was not observed in rs2229338 and rs1059559 before and after multivariate adjustment. These associations were not modified by serum HDL concentration. Furthermore, there were significant interactions between rs2468844 and rs12218 (interaction P<0.001) and rs2229338 (interaction P = 0.001) on carotid IMT. CONCLUSION/SIGNIFICANCE: Both rs12218 of the SAA1 gene and rs2468844 of SAA2 gene are associated with carotid IMT in healthy Han Chinese subjects

Entropies of Negative Incomes, Pareto-Distributed Loss, and Financial Crises

Health monitoring of world economy is an important issue, especially in a time of profound economic difficulty world-wide. The most important aspect of health monitoring is to accurately predict economic downturns. To gain insights into how economic crises develop, we present two metrics, positive and negative income entropy and distribution analysis, to analyze the collective “spatial” and temporal dynamics of companies in nine sectors of the world economy over a 19 year period from 1990–2008. These metrics provide accurate predictive skill with a very low false-positive rate in predicting downturns. The new metrics also provide evidence of phase transition-like behavior prior to the onset of recessions. Such a transition occurs when negative pretax incomes prior to or during economic recessions transition from a thin-tailed exponential distribution to the higher entropy Pareto distribution, and develop even heavier tails than those of the positive pretax incomes. These features propagate from the crisis initiating sector of the economy to other sectors