58 research outputs found

    Tumor-homing cytotoxic human induced neural stem cells for cancer therapy

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    Engineered neural stem cells (NSCs) are a promising approach to treating glioblastoma (GBM). The ideal NSC drug carrier for clinical use should be easily isolated and autologous to avoid immune rejection. We transdifferentiated (TD) human fibroblasts into tumor-homing early-stage induced NSCs (h-iNSCTE), engineered them to express optical reporters and different therapeutic gene products, and assessed the tumor-homing migration and therapeutic efficacy of cytotoxic h-iNSCTE in patient-derived GBM models of surgical and nonsurgical disease. Molecular and functional analysis revealed that our single-factor SOX2 TD strategy converted human skin fibroblasts into h-iNSCTE that were nestin+ and expressed pathways associated with tumor-homing migration in 4 days. Time-lapse motion analysis showed that h-iNSCTE rapidly migrated to human GBM cells and penetrated human GBM spheroids, a process inhibited by blockade of CXCR4. Serial imaging showed that h-iNSCTE delivery of the proapoptotic agent tumor necrosis factor-A-related apoptosis-inducing ligand (TRAIL) reduced the size of solid human GBM xenografts 250-fold in 3 weeks and prolonged median survival from 22 to 49 days. Additionally, h-iNSCTE thymidine kinase/ganciclovir enzyme/prodrug therapy (h-iNSCTE-TK) reduced the size of patient-derived GBM xenografts 20-fold and extended survival from 32 to 62 days. Mimicking clinical NSC therapy, h-iNSCTE-TK therapy delivered into the postoperative surgical resection cavity delayed the regrowth of residual GBMs threefold and prolonged survival from 46 to 60 days. These results suggest that TD of human skin into h-iNSCTE is a platform for creating tumor-homing cytotoxic cell therapies for cancer, where the potential to avoid carrier rejection could maximize treatment durability in human trials

    Periodic and Quasiperiodic Motion of an Elongated Microswimmer in Poiseuille Flow

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    We study the dynamics of a prolate spheroidal microswimmer in Poiseuille flow for different flow geometries. When moving between two parallel plates or in a cylindrical microchannel, the swimmer performs either periodic swinging or periodic tumbling motion. Although the trajectories of spherical and elongated swimmers are qualitatively similar, the swinging and tumbling frequency strongly depends on the aspect ratio of the swimmer. In channels with reduced symmetry the swimmers perform quasiperiodic motion which we demonstrate explicitely for swimming in a channel with elliptical cross section

    Improving the effectiveness of small-holder farm postharvest practices in fiji

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    This paper outlines current postharvest handling practices of five vegetables supply chains in Viti Levu, the Fiji Islands. Domestic-orientated chains involved characteristically low-input production systems, had limited postharvest infrastructure (packing sheds, cool rooms and grading equipment) and reflected inadequate grower and trader postharvest handling knowledge and expertise. Domestic supply chains are often short, with poor and asymmetric communications, discontinuous transport logistics and ineffective postharvest disease-management the major contributors to postharvest losses. Paradoxically, while increasing farm size tended to reflect greater professionalism of production practices, this did not translate to concurrent improvements in postharvest handling. Export-orientated chains involve a much more structured approach to postharvest handling, based on trader and exporter-led interventions. Product consignments are sourced from a large number of growers, graded and packed in a central pack-house and held under cool storage prior to transport. Aspects of a quality management system are evident, with some traders also providing a support services to their contracted growers to improve product quality and supply uniformity

    Lychee (Litchi chinensis Sonn.) pericarp desiccation and the importance of postharvest micro-cracking

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    Lychee fruit are prone to postharvest desiccation, resulting in browning of the pericarp. Microscopic cracks (20–100 μm wide) in the pericarp surface were observed at harvest and had significantly increasing in density 12 h later. Microcracking extended through the sub-epidermal sclerenchyma layer into the mesocarp. Pericarp desiccation occurred prior to crack development, with cracking the result of dehydration rather than the initial cause. No evidence of cuticle thinning was observed prior to micro-cracking, however, localised cuticle deterioration on the protuberance did occur. We believe that initial pericarp desiccation may be the result of high permeability of the cuticle to water vapour, cuticle damage and the presence of lenticels. Although the cracking did not increase the rate of desiccation, micro-cracks may be important in both exposing the underlying anthocyanin-containing mesocarp tissue to further desiccation, and fungal penetration into the pericarp

    Food purchasing behaviors of a remote and rural adult Solomon Islander population

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    The aim of this study was to investigate the food purchasing behaviors of an adult Solomon Islander population within a transitioning food system in Auki, Malaita. Food purchasing behavior measures included; venue type and transportation for purchasing food, previous day expenditure on food purchases, number of weekly shopping experiences for store foods (generally long-life shelf and frozen items) and fresh foods (such as fruits and vegetables and fresh fish) and the importance of factors (i.e., price) on purchasing decisions. One hundred and thirty-three adults (aged 18 to 74 years; female: 63%, males: 37%) completed an interviewer administered questionnaire during December 2018. Food items were primarily sourced from Auki markets (n = 70) and stores (n = 40). Food purchasing differed between fresh and semi-perishable foods (store food). Participants reported similar shopping experiences for store food and fresh food (M = 3.87 and M = 3.25 times a week, respectively) and spending between 1and1 and 200 (M = $56.12) Solomon Island dollars on food in the previous day. The most reported purchased item was white rice (n = 117, 88%), with taste, freshness and family preference the most important factors reported as influencing food purchasing choices. While our findings are from a small sample in Auki, further research could build upon this work by investigating food purchasing behaviors at other times of the year, and more widely in the Solomon Islands and greater Pacific region

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    Flavedo and albedo changes in 'Eureka' lemons caused by static compression and impact loading

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    Mature lemons (Citrus limon (L.) Burm. ‘Eureka') were subjected to increasing compression, impact and static loading, then stored at either 1C, 13C or 20C for 14 or 28 days. Following storage, fruit were assessed for cellular damage associated with the site of loading. Slow compression (1.7cm plunger driven at a loading rate of 200 mm min−1) resulted in cell damage in the mid to lower flavedo tissue. Tissue failure was characterised by cell rupture, with minor cell deformation and compression associated with damage to the oil glands. Impact loading caused relatively little lower flavedo damage, with most of the injury associated with the albedo, the upper flavedo and tissue surrounding the oil glands. Damaged albedo cells formed a distinct zone of ruptured and laterally compressed tissue which increased in area with drop height. Static loading (3.7 kg top weight) resulted in a similar mode of failure to that of impact loading, with extensive cellular damage observed in the lower albedo. Injury was distinct in that cells were not laterally compressed and flavedo damage was far more pronounced

    Fruit canopy position and panicle bagging affects yield and quality of 'Tai So' lychee

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    To determine the potential for fruit bagging to improve the quality of lychee, panicles on the northeast (NE), southeast (SE), southwest (SW) and northwest (NW), and at the top and bottom of the canopy of 12-year-old `Tai So' lychee trees, were enclosed in paper bags at early fruit set, at 1/2–3/4 fruit fill, and just before fruit colouring (corresponding to 80, 42 and 28 days before harvest). At commercial maturity, panicles from the NE and NW aspects and from the upper canopy had the greater number and mass of fruit per panicle, than panicles from the other parts of the canopy. Bagging had no significant (P<0.05) effect on panicle yield. Fruit from the NW aspect were of lower visual quality, due mainly to light and dark brown blemishes on the skin, rather than the colour of the red portion of the skin. Lower canopy and NE fruit were less red (higher hue angle; h°), but there was little effect of canopy height on visual quality. Bagging increased the percentage of fruit in first class, mainly because of increased visual quality of fruit from the NW and SE aspects. The percentage of second class fruit was not affected by bagging, but the percentage rejects was reduced. Unbagged fruit had a lower Chroma (C*) and a higher h°, especially in fruit from the NE. Fruit from the NE and NW aspects and from the lower canopy, had lower brix/acid ratios. Thus, bagging has the potential to improve fruit quality and red colour with no negative impact on yield

    Enzymes associated with blackheart development in pineapple fruit

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    The involvement of browning enzymes, polyphenoloxidase (PPO), peroxidase (POD) and phenylalanine ammonia-lyase (PAL) in blackheart development was investigated in pineapple fruit (Ananas comosus, Smooth Cayenne) following low temperature storage. An increase in PPO activity was related to the incidence of blackheart symptoms, both temporally and spatially. Fruit maturity significantly affected blackheart susceptibility; immature and over-mature fruits developed less blackheart injury than mature fruit. The effect of maturity on blackheart susceptibility was highly correlated to the response of PPO activity to chilling. POD showed no significant change after chilling. Enhanced PAL activity was observed during chilling at 6, 13 and 18 °C. Chilling (6, 13 and 18 °C) also inhibited the increase of ascorbate peroxidase activity observed in the fruit stored continuously at 25 °C, but had less effect on catalase activity. The results indicate that the development of blackheart symptoms in pineapple fruit results from the disturbance of a number of metabolic processes that occur at sub-ambient temperatures
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