Optical coherence tomography enables imaging of tumor initiation in the TAg-RB mouse model of retinoblastoma

PURPOSE: Retinoblastoma is the most common primary intraocular malignancy in children. Although significant advances in treatment have decreased mortality in recent years, morbidity continues to be associated with these therapies, and therefore, there is a pressing need for new therapeutic options. Transgenic mouse models are popular for testing new therapeutics as well as studying the pathophysiology of retinoblastoma. The T-antigen retinoblastoma (TAg-RB) model has close molecular and histological resemblance to human retinoblastoma tumors; these mice inactivate pRB by retinal-specific expression of the Simian Virus 40 T-antigens. Here, we evaluated whether optical coherence tomography (OCT) imaging could be used to document tumor growth in the TAg-RB model from the earliest stages of tumor development. METHODS: The Micron III rodent imaging system was used to obtain fundus photographs and OCT images of both eyes of TAg-RB mice weekly from 2 to 12 weeks of age and at 16 and 20 weeks of age to document tumor development. Tumor morphology was confirmed with histological analysis. RESULTS: Before being visible on funduscopy, hyperreflective masses arising in the inner nuclear layer were evident at 2 weeks of age with OCT imaging. After most of these hyperreflective cell clusters disappeared around 4 weeks of age, the first tumors became visible on OCT and funduscopy by 6 weeks. The masses grew into discrete, discoid tumors, preferentially in the periphery, that developed more irregular morphology over time, eventually merging and displacing the inner retinal layers into the vitreous. CONCLUSIONS: OCT is a non-invasive imaging modality for tracking early TAg-RB tumor growth in vivo. Using OCT, we characterized TAg-positive cells as early as 2 weeks, corresponding to the earliest stages at which tumors are histologically evident, and well before they are evident with funduscopy. Tracking tumor growth from its earliest stages will allow better analysis of the efficacy of novel therapeutics and genetic factors tested in this powerful mouse model

The Human Resource Implications of Plant Shutdowns

Human resource programs that were developed to serve those displaced by plant closings have been fragmented. Participation rates have been low in placement, job search assistance, relocation, and retrain ing programs, and results have not been particularly positive. Great emphasis was placed upon serving those in need when programs did develop. The fragmentation characteristic of previous policy—or nonpolicy— seems to have undergone considerable organization and rationalization with the advent of the Job Training Partnership Act (JTPA) and the association of several major labor-management displaced worker pro grams with the federal-state program. This change tends to emphasize placement and to focus upon training exclusively. As a result, not only will disadvantaged workers compete with displaced workers for training resources and jobs, but participation in programs for displaced workers will be encouraged for those who are most advantaged, thus consigning a large number of less-advantaged displaced workers to underemployment, permanent unemployment, and eventual dependence upon income main tenance.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/67203/2/10.1177_000271628447500106.pd

Kif14 overexpression accelerates murine retinoblastoma development

The mitotic kinesin KIF14 has an essential role in the recruitment of proteins required for the final stages of cytokinesis. Genomic gain and/or overexpression of KIF14 has been documented in retinoblastoma and a number of other cancers, such as breast, lung and ovarian carcinomas, strongly suggesting its role as an oncogene. Despite evidence of oncogenic properties in vitro and in xenografts, Kif14's role in tumor progression has not previously been studied in a transgenic cancer model. Using a novel Kif14 overexpressing, simian virus 40 large T-antigen retinoblastoma (TAg-RB) double transgenic mouse model, we aimed to determine Kif14's role in promoting retinal tumor formation. Tumor initiation and development in double transgenics and control TAg-RB littermates were documented in vivo over a time course by optical coherence tomography, with subsequent ex vivo quantification of tumor burden. Kif14 overexpression led to an accelerated initiation of tumor formation in the TAg-RB model and a significantly decreased tumor doubling time (1.8 vs. 2.9 weeks). Moreover, overall percentage tumor burden was also increased by Kif14 overexpression. These data provide the first evidence that Kif14 can promote tumor formation in susceptible cells in vivo

A simple optical coherence tomography quantification method for choroidal neovascularization

Purpose: Therapeutic efficacy is routinely assessed by measurement of lesion size using flatmounted choroids and confocal microscopy in the laser-induced choroidal neovascularization (L-CNV) rodent model. We investigated whether optical coherence tomography (OCT) quantification, using an ellipsoid volume measurement, was comparable to standard ex vivo evaluation methods for this model and whether this approach could be used to monitor treatment-related lesion changes. Methods: Bruch's membrane was ruptured by argon laser in the dilated eyes of C57BL/6J mice, followed by intravitreal injections of anti-VEGF164 or vehicle, or no injection. In vivo OCT images were acquired using Micron III or InVivoVue systems at 7, 10, and/or 14 days post-laser and neovascular lesion volume was calculated as an ellipsoid. Subsequently, lesion volume was compared to that calculated from confocal Z-stack images of agglutinin-stained choroidal flatmounts. Results: Ellipsoid volume measurement of orthogonal 2-dimensional OCT images obtained from different imaging systems correlated with ex vivo lesion volumes for L-CNV (Spearman's ρ=0.82, 0.75, and 0.82 at days 7, 10, and 14, respectively). Ellipsoid volume calculation allowed temporal monitoring and evaluation of CNV lesions in response to antivascular endothelial growth factor treatment. Conclusions: Ellipsoid volume measurements allow rapid, quantitative use of OCT for the assessment of CNV lesions in vivo. This novel method can be used with different OCT imaging systems with sensitivity to distinguish between treatment conditions. It may serve as a useful adjunct to the standard ex vivo confocal quantification, to assess therapeutic efficacy in preclinical models of CNV, and in models of other ocular diseases

Additive manufacturing enabling W-SiC and W-ZrB2-SiC heterogeneous materials

Please click Additional Files below to see the full abstract

A New View of Coastal Oceans From the Space Station

No abstract available

Effet de l'implantation d'une unité de méthanisation sur l'impact environnemental de la production de porc : cas d'une ferme en Bretagne

International audienceEffet de l'implantation d'une unité de méthanisation sur l'impact environnemental de la production de porc : cas d'une ferme en Bretagne. 47èmes Journées de la Recherche PorcineEffet de l'implantation d'une unité de méthanisation sur l'impact environnemental de la production de porc : cas d'une ferme en Bretagne. La méthanisation se développe en France dans un objectif d'atténuation des émissions de gaz à effet de serre (GES) et de production d'énergie renouvelable. Néanmoins, son développement doit s'accompagner d'un suivi environnemental notamment au niveau de la qualité des sols. L'objectif de ce travail était d'évaluer par analyse du cycle de vie (ACV) les conséquences environnementales de la mise en place d'un méthaniseur en codigestion sur une exploitation porcine en regardant plus particulièrement les effets sur la teneur en matière organique du sol. L'étude porte sur la comparaison de deux scénarios basés sur un cas type d'exploitation porcine de 225 truies produisant 4800 porcs par an, avec 1) un stockage et un épandage classique des effluents (scénario REF) ou 2) l'implantation d'un méthaniseur de 50 KW (scénario METH). L'unité fonctionnelle choisie est le kg de porc vif produit. Les modifications de l'assolement associées au scénario METH ont été prises en compte (production de triticale et d'orge en interculture pour alimenter le méthaniseur). Les deux scénarios ont été analysés par ACV en incluant des indicateurs de qualité du sol. L'analyse montre que l'implantation d'un méthaniseur sur l'exploitation réduit l'impact changement climatique de 2% (1,86 vs 1,90 kg éq. CO 2 ./kg de poids vif) et l'utilisation d'énergie de 8% (10,9 MJ/kg vs 11,8 MJ/kg). La séquestration de carbone dans le sol augmente dans les deux scénarios mais elle est plus importante pour le scénario REF (0,102 kg vs. 0,083 kg C/kg de porc). Elle atteint respectivement 0,191 et 0,166 kg C/kg de porc pour REF et METH, si toute la paille retourne au sol. Toutefois, la qualité de la matière organique contenue dans le digestat doit être caractérisée plus précisément pour pouvoir conclure sur l'impact potentiel de la séquestration du carbone. Effect of on-farm biogas production on impacts of pig production in Brittany, France For the past ten years, anaerobic digestion has developed in France for GHG mitigation and renewable energy production. However, change in soil organic matter (SOM) is another hotspot indicator for bioenergy produced from biomass by anaerobic digestion (AD). The aim of this work was to assess the influence of on-farm co-digestion of pig slurry to produce bioenergy on environmental impacts of pig production from a life cycle perspective. We compared two scenarios: (1) standard manure storage and spreading on a representative pig farm in Brittany (REF scenario) and (2) the same pig farm with a 50 kW AD plant. The functional unit was one kilogram of pig live weight produced, at the farm gate. The representative farm produces 4800 pigs per year with 225 productive sows. In the AD scenario, oats and triticale are grown as intercrops to feed the AD plant. Life cycle assessment of the two scenarios showed lower environmental impacts of the farm with AD. The introduction of an AD plant reduced climate change impact by 2% (REF: 1.90 kg CO 2-eq./kg; AD: 1.86 kg CO 2-eq./kg) and cumulative energy demand by 8% (REF: 11.8 MJ/kg; AD: 10.9 MJ/kg). SOM was sequestered in both scenarios, but the REF scenario sequestered more (0.102 kg C/kg vs. 0.083 kg C/kg for AD). Sequestration increased to 0.191 and 0.166 kg C/kg in REF and AD scenarios, respectively, if all straw was returned to the soil. C mineralization characteristics of digestate should be known more accurately before drawing conclusions about the potential impact of SOM change

A novel small molecule ameliorates ocular neovascularisation and synergises with anti-VEGF therapy

Ocular neovascularisation underlies blinding eye diseases such as retinopathy of prematurity, proliferative diabetic retinopathy, and wet age-related macular degeneration. These diseases cause irreversible vision loss, and provide a significant health and economic burden. Biologics targeting vascular endothelial growth factor (VEGF) are the major approach for treatment. However, up to 30% of patients are non-responsive to these drugs and they are associated with ocular and systemic side effects. Therefore, there is a need for small molecule ocular angiogenesis inhibitors to complement existing therapies. We examined the safety and therapeutic potential of SH-11037, a synthetic derivative of the antiangiogenic homoisoflavonoid cremastranone, in models of ocular neovascularisation. SH-11037 dose-dependently suppressed angiogenesis in the choroidal sprouting assay ex vivo and inhibited ocular developmental angiogenesis in zebrafish larvae. Additionally, intravitreal SH-11037 (1 μM) significantly reduced choroidal neovascularisation (CNV) lesion volume in the laser-induced CNV mouse model, comparable to an anti-VEGF antibody. Moreover, SH-11037 synergised with anti-VEGF treatments in vitro and in vivo. Up to 100 μM SH-11037 was not associated with signs of ocular toxicity and did not interfere with retinal function or pre-existing retinal vasculature. SH-11037 is thus a safe and effective treatment for murine ocular neovascularisation, worthy of further mechanistic and pharmacokinetic evaluation