6,286 research outputs found

    Immunity toward H1N1 influenza hemagglutinin of historical and contemporary strains suggests protection and vaccine failure

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    Evolution of H1N1 influenza A outbreaks of the past 100 years is interesting and significantly complex and details of H1N1 genetic drift remains unknown. Here we investigated the clinical characteristics and immune cross-reactivity of significant historical H1N1 strains. We infected ferrets with H1N1 strains from 1943, 1947, 1977, 1986, 1999, and 2009 and showed each produced a unique clinical signature. We found significant cross-reactivity between viruses with similar HA sequences. Interestingly, A/FortMonmouth/1/1947 antisera cross-reacted with A/USSR/90/1977 virus, thought to be a 1947 resurfaced virus. Importantly, our immunological data that didn't show cross-reactivity can be extrapolated to failure of past H1N1 influenza vaccines, ie. 1947, 1986 and 2009. Together, our results help to elucidate H1N1 immuno-genetic alterations that occurred in the past 100 years and immune responses caused by H1N1 evolution. This work will facilitate development of future influenza therapeutics and prophylactics such as influenza vaccines.published_or_final_versio

    Recent Progress in Phage Therapy to Modulate Multidrug-Resistant Acinetobacter baumannii, Including in Human and Poultry

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    Acinetobacter baumannii is a multidrug-resistant and invasive pathogen associated with the etiopathology of both an increasing number of nosocomial infections and is of relevance to poultry production systems. Multidrug-resistant Acinetobacter baumannii has been reported in connection to severe challenges to clinical treatment, mostly due to an increased rate of resistance to carbapenems. Amid the possible strategies aiming to reduce the insurgence of antimicrobial resistance, phage therapy has gained particular importance for the treatment of bacterial infections. This review summarizes the different phage-therapy approaches currently in use for multiple-drug resistant Acinetobacter baumannii, including single phage therapy, phage cocktails, phage–antibiotic combination therapy, phage-derived enzymes active on Acinetobacter baumannii and some novel technologies based on phage interventions. Although phage therapy represents a potential treatment solution for multidrug-resistant Acinetobacter baumannii, further research is needed to unravel some unanswered questions, especially in regard to its in vivo applications, before possible routine clinical use

    Coexistence of the topological state and a two-dimensional electron gas on the surface of Bi2Se3

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    Topological insulators are a recently discovered class of materials with fascinating properties: While the inside of the solid is insulating, fundamental symmetry considerations require the surfaces to be metallic. The metallic surface states show an unconventional spin texture, electron dynamics and stability. Recently, surfaces with only a single Dirac cone dispersion have received particular attention. These are predicted to play host to a number of novel physical phenomena such as Majorana fermions, magnetic monopoles and unconventional superconductivity. Such effects will mostly occur when the topological surface state lies in close proximity to a magnetic or electric field, a (superconducting) metal, or if the material is in a confined geometry. Here we show that a band bending near to the surface of the topological insulator Bi2_2Se3_3 gives rise to the formation of a two-dimensional electron gas (2DEG). The 2DEG, renowned from semiconductor surfaces and interfaces where it forms the basis of the integer and fractional quantum Hall effects, two-dimensional superconductivity, and a plethora of practical applications, coexists with the topological surface state in Bi2_2Se3_3. This leads to the unique situation where a topological and a non-topological, easily tunable and potentially superconducting, metallic state are confined to the same region of space.Comment: 12 pages, 3 figure

    Towards a career in bioinformatics

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    The 2009 annual conference of the Asia Pacific Bioinformatics Network (APBioNet), Asia's oldest bioinformatics organisation from 1998, was organized as the 8th International Conference on Bioinformatics (InCoB), Sept. 9-11, 2009 at Biopolis, Singapore. InCoB has actively engaged researchers from the area of life sciences, systems biology and clinicians, to facilitate greater synergy between these groups. To encourage bioinformatics students and new researchers, tutorials and student symposium, the Singapore Symposium on Computational Biology (SYMBIO) were organized, along with the Workshop on Education in Bioinformatics and Computational Biology (WEBCB) and the Clinical Bioinformatics (CBAS) Symposium. However, to many students and young researchers, pursuing a career in a multi-disciplinary area such as bioinformatics poses a Himalayan challenge. A collection to tips is presented here to provide signposts on the road to a career in bioinformatics. An overview of the application of bioinformatics to traditional and emerging areas, published in this supplement, is also presented to provide possible future avenues of bioinformatics investigation. A case study on the application of e-learning tools in undergraduate bioinformatics curriculum provides information on how to go impart targeted education, to sustain bioinformatics in the Asia-Pacific region. The next InCoB is scheduled to be held in Tokyo, Japan, Sept. 26-28, 2010

    Learning Visual Context by Comparison

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    Finding diseases from an X-ray image is an important yet highly challenging task. Current methods for solving this task exploit various characteristics of the chest X-ray image, but one of the most important characteristics is still missing: the necessity of comparison between related regions in an image. In this paper, we present Attend-and-Compare Module (ACM) for capturing the difference between an object of interest and its corresponding context. We show that explicit difference modeling can be very helpful in tasks that require direct comparison between locations from afar. This module can be plugged into existing deep learning models. For evaluation, we apply our module to three chest X-ray recognition tasks and COCO object detection & segmentation tasks and observe consistent improvements across tasks. The code is available at https://github.com/mk-minchul/attend-and-compare.Comment: ECCV 2020 spotlight pape

    DNA topoisomerases participate in fragility of the oncogene RET

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    Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication

    Rudimentary G-Quadruplex-Based Telomere Capping In Saccharomyces Cerevisiae

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    Telomere capping conceals chromosome ends from exonucleases and checkpoints, but the full range of capping mechanisms is not well defined. Telomeres have the potential to form G-quadruplex (G4) DNA, although evidence for telomere G4 DNA function in vivo is limited. In budding yeast, capping requires the Cdc13 protein and is lost at nonpermissive temperatures in cdc13-1 mutants. Here, we use several independent G4 DNA-stabilizing treatments to suppress cdc13-1 capping defects. These include overexpression of three different G4 DNA binding proteins, loss of the G4 DNA unwinding helicase Sgs1, or treatment with small molecule G4 DNA ligands. In vitro, we show that protein-bound G4 DNA at a 3\u27 overhang inhibits 5\u27-\u3e 3\u27 resection of a paired strand by exonuclease I. These findings demonstrate that, at least in the absence of full natural capping, G4 DNA can play a positive role at telomeres in vivo
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