Charge structure in volcanic plumes: a comparison of plume properties predicted by an integral plume model to observations of volcanic lightning during the 2010 eruption of Eyjafjallajökull, Iceland

Cancer is a heterogeneous disease with different combinations of genetic alterations driving its development in different individuals. We introduce CoMEt, an algorithm to identify combinations of alterations that exhibit a pattern of mutual exclusivity across individuals, often observed for alterations in the same pathway. CoMEt includes an exact statistical test for mutual exclusivity and techniques to perform simultaneous analysis of multiple sets of mutually exclusive and subtype-specific alterations. We demonstrate that CoMEt outperforms existing approaches on simulated and real data. We apply CoMEt to five different cancer types, identifying both known cancer genes and pathways, and novel putative cancer genes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13059-015-0700-7) contains supplementary material, which is available to authorized users

Antibody-mediated therapy against HIV/AIDS: Where are we standing now?

Acquired immunodeficiency syndrome (AIDS) cases are on the rise globally. To date, there is still no effective measure to eradicate the causative agent, human immunodeficiency virus (HIV). Highly active antiretroviral therapy (HAART) is being used in HIV/AIDS management, but it results in long-term medication and has major drawbacks such as multiple side effects, high cost, and increasing the generation rate of escape mutants. In addition, HAART does not control HIV-related complications, and hence more medications and further management are required. With this, other alternatives are urgently needed. In the past, small molecule inhibitors have shown potent antiviral effects, and some of them are now being evaluated in clinical trials. The challenges in developing these small molecules for clinical use include the off-target effect, poor stability, and low bioavailability. On the other hand, antibody-mediated therapy has emerged as an important therapeutic modality for anti-HIV therapeutics development. Many antiviral antibodies, namely, broad neutralizing antibodies (bnAbs) against multiple strains of HIV, have shown promising effects in vitro and in animal studies; further studies are ongoing in clinical trials to evaluate their uses in clinical applications. This short review aims to discuss the current development of therapeutic antibodies against HIV and the challenges in adopting them for clinical use

Distributed GIS for Monitoring and Modeling Urban Air Quality

The progress of technology has made the measurement of air quality and the simulation of complex air pollution models both feasible and cost-effective. However, there is a long way to go in terms of facilitating widespread access to the data and models, and linking the monitoring of trace gases with specific urban activities and land use that might be controllable. As part of a NASA-funded project, we are working with scientists and engineers to design and test a distributed GIS infrastructure for studying such "urban respiration" phenomena. Measurements of trace gases within a metropolitan area (from mobile and fixed instruments) are geo-referenced, time-stamped, and stored in a relational database server (Oracle). GIS services (using ArcInfo and ArcView) are connected to the database so that subsets of the trace gas measurements can be extracted and converted on-the-fly into GIS data layers. These subsets (by location, date, and time-of-day) can be displayed and cross-referenced with other layers such as weather conditions, land use and cover, topography, hydrography, demography, and congestion levels of road networks. A web-based interface (using ArcView Internet Map Server) allows research team members at different locations to query, visualize, and process the cross-referenced data layers in order to generate surface level estimates of initial conditions for use in the air quality models.NAS

Epstein-Barr Virus as a promising immunotherapeutic target for nasopharyngeal carcinoma treatment

Epstein-Barr virus (EBV) is a pathogen that infects more than 90% of global human population. EBV primarily targets Blymphocytes and epithelial cells while some of them infect monocyte/macrophage, T-lymphocytes, and dendritic cells (DCs). EBV infection does not cause death by itself but the infection has been persistently associated with certain type of cancers such as nasopharyngeal carcinoma (NPC), Burkitt’s lymphoma (BL), and Hodgkin’s lymphoma (HL). Recent findings have shown promise on targeting EBV proteins for cancer therapy by immunotherapeutic approach. Some studies have also shown the success of adopting EBV-based therapeutic vaccines for the prevention of EBV-associated cancer particularly on NPC. In-depth investigations are in progress to refine the current therapeutic and vaccination strategies. In present review, we discuss the highly potential EBV targets for NPC immunotherapy and therapeutic vaccine development aswell as addressing the underlying challenges in the process of bringing the therapy and vaccination from the bench to bedside

Review of current cell-penetrating antibody developments for HIV-1 therapy

The discovery of highly active antiretroviral therapy (HAART) in 1996 has significantly reduced the global mortality and morbidity caused by the acquired immunodeficiency syndrome (AIDS). However, the therapeutic strategy of HAART that targets multiple viral proteins may render off-target toxicity and more importantly results in drug-resistant escape mutants. These have been the main challenges for HAART and refinement of this therapeutic strategy is urgently needed. Antibody-mediated treatments are emerging therapeutic modalities for various diseases. Most therapeutic antibodies have been approved by Food and Drug Administration (FDA) mainly for targeting cancers. Previous studies have also demonstrated the promising effect of therapeutic antibodies against HIV-1, but there are several limitations in this therapy, particularly when the viral targets are intracellular proteins. The conventional antibodies do not cross the cell membrane, hence, the pathogenic intracellular proteins cannot be targeted with this classical therapeutic approach. Over the years, the advancement of antibody engineering has permitted the therapeutic antibodies to comprehensively target both extra- and intra-cellular proteins in various infections and diseases. This review aims to update on the current progress in the development of antibody-based treatment against intracellular targets in HIV-1 infection. We also attempt to highlight the challenges and limitations in the development of antibody-based therapeutic modalities against HIV-1

Cryopreservation of Umbilical Cord Tissue for Stem Cell Harvesting

Stem cell transplantation has become an important process used to treat patients with bone marrow diseases. When implanted into patients, stem cells from the umbilical cord have been found to successfully proliferate as new neurons and glia, thereby improving the patients? health. Neurons and glia are imperative for the health and normal function of our nervous system. Neurons are electrically active cells that can produce action potentials to transmit signals based on electrochemical impulses. Glia, which comprise a large part of our nervous systems (90% of the brain alone), were once dismissed as mere padding in the nervous system. However, it is now known that they are actually an integral component of the system, serving to facilitate and ensure the proper transmission of signals between neurons. Damage to or loss of neural cells, whether due to physical injury, removal (as in the case of cancer) or diseases such as Motor Neuron Disease (MND) and Parkinson?s disease is severely detrimental to one?s health. Using current tissue engineering technology, stem cells harvested from the matrix of the umbilical cord (known as Wharton?s Jelly), may be differentiated into neurons or glia, effectively replacing those that were lost or damaged. To ensure biocompatibility, umbilical cord matrix cells from direct relatives are used. Therefore, cryopreservation of these cells is imperative to the stem cell treatment to be used in the future. Our goal is to use FIDAP and GAMBIT software solutions and mesh to compare the effectiveness of glycerol, propylene glycol, and DMSO, three commonly used cryopreservatives, in order to determine the cryopreservation agent that will maximize viability of umbilical cord stem cells

Hevea genetic transformation using a single-chain variable fragment (scFv) specific to cassiicolin, the causal agent of Corynespora leaf disease

The pathogenic fungus Corynespora cassiicola a serious threat to rubber trees (Hevea brasiliensis); the infected leaves develop necrotic lesions and abscise, leaving the tree unproductive. The destructiveness of C. cassiicola has been largely attributed to cassiicolin, a secreted protein toxin of the fungus. Recombinant antibody technology coupled to genetic transformation offer hope to curtail the disease in Hevea. Single chain variable fragment (scFv) specific to cassiicolin could bind and deactivate the toxin in genetically modified rubber trees that harbour the functional antibody gene. A scFv phage library was constructed from cassiicolin immunized Balb/C mice spleen IgG heavy and light variable chains. Biopanning of the phage library yielded a scFv clone with high specificity to cassiicolin. Nucleotide sequence and deduced amino acid sequence information of the scFv were obtained. The hemagglutinin (HA) tagged scFv expressed in Escherichia coli is discerned as a band at circa 30 kDa on SDS-PAGE. The corresponding band was detected by anti-HA IgG on a Western immunoblot of the gel. Homology-based modelling was employed to create three-dimensional structures of the scFv antibody and cassiicolin, and binding (docking) of the antibody to the toxin antigen was simulated. Furthermore, deactivation of cassiicolin by the scFv was demonstrated by detached leaf bio-assay on selected susceptible Hevea clones. Efforts are underway to genetically transform Hevea clones with the cassiicolin-specific scFv gene to enhance resistance to Corynespora leaf disease. (Texte intégral

Pathogenic role of exosomes in Epstein-Barr Virus (EBV)-associated cancers

Exosomes are 40- to 100-nm membrane-bound small vesicles that carry a great variety of cellular cargoes including proteins, DNA, messenger RNAs (mRNAs), and microRNAs (miRNAs). These nanovesicles are detected in various biological fluids such as serum, urine, saliva, and seminal fluids. Exosomes serve as key mediators in intercellular communication by facilitating the transfer and exchange of cellular components from cells to cells. They contain various pathogenic factors whereby their adverse effects have been implicated in multiple viral infections and cancers. Interestingly, accumulating evidences showed that exosomes derived from tumour viruses or oncoviruses, exacerbate virus-associated cancers by remodelling the tumour microenvironment. In this review, we summarize the contributing factors of Epstein-Barr virus (EBV) products-containing exosomes in viral pathogenesis and their potential implications in EBV-driven malignancies. Understanding the biological role of these exosomes in the disease would undoubtedly boost the development of a more comprehensive strategy to combat EBV-associated cancers and to better predict the therapeutic outcomes. Furthermore, we also highlight the potentials and challenges of EBV products-containing exosomes being employed as diagnostic markers and therapeutic targets for EBV-related cancers. Since these aspects are rather underexplored, we attempt to underline interesting areas that warrant further investigations in the future

Molecular typing among poultry isolates of Salmonella agona by PCR-based techniques and pulsed field gel electrophoresis (PFGE)

Nine genomic DNA of Salmonella agona isolated from poultry sources were characterised by three variations of PCR-based techniques [polymerase chain reaction (PCR)-ribotyping, enterobacterial repetitive intergenic consensuspolymerase chain reaction (ERIC-PCR), and random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR)] and pulsed field gel electrophoresis (PFGE). These isolates originated from three different states of Peninsular Malaysia (Pulau Pinang, Negeri Sembilan and Selangor). The results of PCR-ribotyping, ERIC-PCR, RADP-PCR and PFGE to differentiate between nine isolates of S. agona were compared. The isolates were separated into three different genome types by PCR-ribotyping, nine and eight genome types by ERIC-PCR and PFGE, respectively