Analogue peptides for the immunotherapy of human acute myeloid leukemia

Accepted manuscript. The final publication is available at: http://link.springer.com/article/10.1007%2Fs00262-015-1762-9The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies

Rapid Susceptibility Testing and Microcolony Analysis of Candida spp. Cultured and Imaged on Porous Aluminum Oxide

Contains fulltext : 124300.pdf (publisher's version ) (Open Access)BACKGROUND: Acquired resistance to antifungal agents now supports the introduction of susceptibility testing for species-drug combinations for which this was previously thought unnecessary. For pathogenic yeasts, conventional phenotypic testing needs at least 24 h. Culture on a porous aluminum oxide (PAO) support combined with microscopy offers a route to more rapid results. METHODS: Microcolonies of Candida species grown on PAO were stained with the fluorogenic dyes Fun-1 and Calcofluor White and then imaged by fluorescence microscopy. Images were captured by a charge-coupled device camera and processed by publicly available software. By this method, the growth of yeasts could be detected and quantified within 2 h. Microcolony imaging was then used to assess the susceptibility of the yeasts to amphotericin B, anidulafungin and caspofungin (3.5 h culture), and voriconazole and itraconazole (7 h culture). SIGNIFICANCE: Overall, the results showed good agreement with EUCAST (86.5% agreement; n = 170) and E-test (85.9% agreement; n = 170). The closest agreement to standard tests was found when testing susceptibility to amphotericin B and echinocandins (88.2 to 91.2%) and the least good for the triazoles (79.4 to 82.4%). Furthermore, large datasets on population variation could be rapidly obtained. An analysis of microcolonies revealed subtle effects of antimycotics on resistant strains and below the MIC of sensitive strains, particularly an increase in population heterogeneity and cell density-dependent effects of triazoles. Additionally, the method could be adapted to strain identification via germ tube extension. We suggest PAO culture is a rapid and versatile method that may be usefully adapted to clinical mycology and has research applications

Soil–strain compatibility: the key to effective use of arbuscular mycorrhizal inoculants?

Consistency of response to arbuscular mycorrhizal (AM) inoculation is required for efficient use of AM fungi in plant production. Here, we found that the response triggered in plants by an AM strain depends on the properties of the soil where it is introduced. Two data sets from 130 different experiments assessing the outcome of a total of 548 replicated single inoculation trials conducted either in soils with a history of (1) high input agriculture (HIA; 343 replicated trials) or (2) in more pristine soils from coffee plantations (CA; 205 replicated trials) were examined. Plant response to inoculation with different AM strains in CA soils planted with coffee was related to soil properties associated with soil types. The strains Glomus fasciculatum-like and Glomus etunicatum-like were particularly performant in soil relatively rich in nutrients and organic matter. Paraglomus occultum and Glomus mosseae-like performed best in relatively poor soils, and G. mosseae and Glomus manihotis did best in soils of medium fertility. Acaulospora scrobiculata, Diversispora spurca, G. mosseae-like, G. mosseae and P. occultum stimulated coffee growth best in Chromic, Eutric Alluvial Cambisol, G. fasciculatum-like and G. etunicatum-like in Calcaric Cambisol and G. manihotis, in Chromic, Eutric Cambisols. Acaulospora scrobiculata and Diversispora spurca strains performed best in Chromic Alisols and Rodic Ferralsols. There was no significant relationship between plant response to AM fungal strains and soil properties in the HIA soil data set, may be due to variation induced by the use of different host plant species and to modification of soil properties by a history of intensive production. Consideration of the performance of AM fungal strains in target soil environments may well be the key for efficient management of the AM symbiosis in plant production

Erythrocyte Transketolase Activity, Markers of Cardiac Dysfunction and the Diagnosis of Infantile Beriberi

Infantile beriberi, or clinical thiamin (vitamin B1) deficiency in infants, is a forgotten disease in Asia, where ∼100 years ago it was a major public health problem. Children aged ∼2–3 months present in cardiac failure but usually rapidly improve if given thiamin injections. It remains relatively common in Vientiane, Lao PDR (Laos) probably because of prolonged intra- and post-partum maternal food avoidance behaviours. There has been very little recent research on the best diagnostic techniques. We conducted a case control study of 47 infants with beriberi and age-matched afebrile and febrile controls in Vientiane. The conventional measures of thiamin deficiency, basal and activated erythrocyte transketolase activities (ETK) and activation (α) coefficients, were assayed along with three markers of cardiac dysfunction - plasma brain natriuretic peptide, N-terminal pro-brain natriuretic peptide, and troponin T. Basal ETK was a better biochemical marker of infantile beriberi than the activation coefficient. Raised plasma troponin T may be a useful indicator of infantile beriberi in babies at risk and in the absence of other evident causes

Marine Tar Residues: a Review

Abstract Marine tar residues originate from natural and anthropogenic oil releases into the ocean environment and are formed after liquid petroleum is transformed by weathering, sedimentation, and other processes. Tar balls, tar mats, and tar patties are common examples of marine tar residues and can range in size from millimeters in diameter (tar balls) to several meters in length and width (tar mats). These residues can remain in the ocean envi-ronment indefinitely, decomposing or becoming buried in the sea floor. However, in many cases, they are transported ashore via currents and waves where they pose a concern to coastal recreation activities, the seafood industry and may have negative effects on wildlife. This review summarizes the current state of knowledge on marine tar residue formation, transport, degradation, and distribution. Methods of detection and removal of marine tar residues and their possible ecological effects are discussed, in addition to topics of marine tar research that warrant further investigation. Emphasis is placed on ben-thic tar residues, with a focus on the remnants of the Deepwater Horizon oil spill in particular, which are still affecting the northern Gulf of Mexico shores years after the leaking submarine well was capped

Cell culture processes for the production of viral vectors for gene therapy purposes

Gene therapy is a promising technology for the treatment of several acquired and inherited diseases. However, for gene therapy to be a commercial and clinical success, scalable cell culture processes must be in place to produce the required amount of viral vectors to meet market demand. Each type of vector has its own distinct characteristics and consequently its own challenges for production. This article reviews the current technology that has been developed for the efficient, large-scale manufacture of retrovirus, lentivirus, adenovirus, adeno-associated virus and herpes simplex virus vectors