Mapping Protein Interactions between Dengue Virus and Its Human and Insect Hosts

Dengue virus (DENV) represents a major disease burden in tropical and subtropical regions of the world, and has shown an increase in the number of cases in recent years. DENV is transmitted to humans through the bite of an infected mosquito, typically Aedes aegypti, after which it begins the infection and replication lifecycle within human cells. To perform the molecular functions required for invasion, replication, and spread of the virus, proteins encoded by DENV must interact with and alter the behavior of protein networks in both of these hosts. In this work, we used a computational method based on protein structures to predict interactions between DENV and its human and insect hosts. We predict numerous interactions, with many involved in known cell death, stress, and immune system pathways. Further investigation of these predicted protein-protein interactions should provide targets to combat the clinical manifestations of this disease in humans as well as points of intervention focused within the mosquito vector

Preclinical mouse models for BRCA1-associated breast cancer

A substantial part of all hereditary breast cancer cases is caused by BRCA1 germline mutations. In this review, we will discuss the insights into BRCA1 functions that we obtained from mouse models with conventional and conditional mutations in Brca1. The most advanced models closely resemble human BRCA1-related breast cancer and may therefore be useful for addressing clinically relevant questions

Cytoplasmic levels of cFLIP determine a broad susceptibility of breast cancer stem/progenitor-like cells to TRAIL

Background The clinical application of TRAIL receptor agonists as a novel cancer therapy has been tempered by heterogeneity in tumour responses. This is illustrated in breast cancer, where TRAIL is cytotoxic in cell lines of mesenchymal origin but refractory in lines with an epithelial-like phenotype. However, it is now evident that intra-tumour heterogeneity includes a minority subpopulation of tumour-initiating stem/progenitor-like cells (CSCs) that possess mesenchymal characteristics. We hypothesised therefore that TRAIL may target these phenotypically distinct CSC-like cells that are common to most - if not all - breast cancers, thus impacting on the source of malignancy in a much broader range of breast tumour subtypes than previously envisaged. Methods We used colony formation, tumoursphere, flow cytometry and xenograft tumour initiation assays to observe the TRAIL sensitivity of CSC-like cells in a panel of two mesenchymal-like (TRAIL-sensitive) and four epithelial-like (TRAIL-resistant) breast cancer cell lines. Subcellular levels of the endogenous TRAIL inhibitor, cFLIP, were determined by western blot and immunofluorescence microscopy. The effect of the subcellular redistribution of cFLIP on TRAIL sensitivity and Wnt signalling was determined using cFLIP localisation mutants and the TOPFlash reporter assay respectively. Results TRAIL universally suppressed the clonal expansion of stem/progenitors in all six of the breast cancer cell lines tested, irrespective of their phenotype or overall sensitivity to TRAIL. A concomitant reduction in tumour initiation was confirmed in the TRAIL-resistant epithelial cell line, MCF-7, following serial dilution xenotransplantation. Furthermore TRAIL sensitivity of breast CSCs was inversely proportional to the relative cytoplasmic levels of cFLIP while overexpression of cFLIP in the cytosol using subcellular localization mutants of cFLIP protected these cells from cytotoxicity. The accumulation of nuclear cFLIP on the other hand did not influence TRAIL cytotoxicity but instead promoted Wnt-dependent signalling. Conclusion These data propose a novel role for TRAIL as a selective CSC agent with a broad specificity for both epithelial and mesenchymal breast tumour subtypes. Furthermore we identify a dual role for cFLIP in the maintenance of breast CSC viability, dependent upon its subcellular distribution

Ecological energy requirements of the green mussel, perna viridis linnaeus from ennore estuary, madras

Ecological energies of growth and respiration were computed for individuals of the tropical intertidal green mussel, Perna viridis L. from Ennore estuary Madras for the period 1974-1975.Von Bertalanffy growth curve was fitted to data obtained from rearing marked animals in the field. Perna viridis has a higher rate of growth than all other mussels studied so far.Growth efficiency was computed for mussels of various sizes and the values were 56, 41, 32 and 19% for 2, 40, 80 and 120 mm sized mussels respectively. [NOT CONTROLLED OCR]L'énergie écologique de croissance et de respiration est calculée pour la moule verte du milieu intertidal tropical, Perna viridis L. pendant la période 1974-1975.La courbe de von Bertalanffy a été ajustée à partir des résultats obtenus à l'aide d'une expérience de marquage. Nous avons trouvé que les taux de croissance des moules tropicales étaient beaucoup plus élevés que ceux décrits pour les autres espèces de moules.Le calcul de l'efficacité de croissance nous a donné les résultats suivants : 56, 41, 32 et 19% respectivement pour les moules ayant une longueur de 2, 40, 80 et 120 mm. [OCR NON CONTRÔLE

Reproductive strategies and energy sources fuelling reproductive growth in a protracted spawner

Most marine invertebrates experience variable environments and for broadcast spawners, fertilisation success increases with greater synchronisation of spawning, so a capital breeding strategy is predicted. However, this prediction should be tested for species with protracted breeding seasons, since it is not clear how reproduction is fuelled over several consecutive months of spawning. The simultaneous hermaphrodite scallop <i>Pecten fumatus</i> was used to test the hypothesis that protracted spawning is supported by both capital and income strategies, depending on the state of energy reserves and food availability at the time of oocyte maturation. The study was carried out in Great Bay, Tasmania, Australia (147.335W, 43.220S) in 2010/2011. The use of glycogen, protein and lipid in the muscle, gonad, and digestive gland was examined, along with the role of atretic eggs as an alternative energy source for oogenesis and maturation. The reproductive stage of an individual was determined using only the ovaries. <i>P. fumatus</i> uses a capital breeding strategy early in the reproductive cycle during winter and spring (August–October) with muscle glycogen and protein and digestive gland lipid providing energy for oogenesis. Given there was no evidence of energy stores being used later in the reproductive cycle in late spring and summer (November–March), when less food was available for direct fuelling of reproduction, it appears that metabolites produced from oocyte lysis may have fuelled oogenesis. Recycling of energy from oocyte resorption must be considered as part of the strategy of energy use to fuel reproduction in marine invertebrates