Transcriptomic Profiles of CD47 in Breast Tumors Predict Outcome and Are Associated with Immune Activation

Targeting the innate immune system has attracted attention with the development of anti- CD47 antibodies. Anti-CD47 antibodies block the inhibition of the phagocytic activity of macrophages caused by the up-regulation of CD47 on tumor cells. In this study, public genomic data was used to identify genes highly expressed in breast tumors with elevated CD47 expression and analyzed the association between the presence of tumor immune infiltrates and the expression of the selected genes. We found that 142 genes positively correlated with CD47, of which 83 predicted favorable and 32 detrimental relapse-free survival (RFS). From those associated with favorable RFS, we selected the genes with immunologic biological functions and defined a CD47-immune signature composed of PTPRC, HLA-E, TGFBR2, PTGER4, ETS1, and OPTN. In the basal-like and HER2+ breast cancer subtypes, the expression of the CD47-immune signature predicted favorable outcome, correlated with the presence of tumor immune infiltrates, and with gene expression signatures of T cell activation. Moreover, CD47 up-regulated genes associated with favorable survival correlated with pro-tumoral macrophages. In summary, we described a CD47-immune gene signature composed of 6 genes associated with favorable prognosis, T cell activation, and pro-tumoral macrophages in breast cancer tumors expressing high levels of CD47.     

Maize and pigeon pea sole crop and intercrop nutrient response functions for Tanzania

The development of ecological circular agriculture has been highly encouraged by the Chinese government to recycle agricultural wastes, reduce mineral fertilizer input, and protect the environment. Biogas slurry, a byproduct of biogas engineering developed in rural areas of China, could be used as N fertilizer for crop growth. The field experiments were conducted in 2014 and 2015 to study the plant growth responses and environmental impacts of applying biogas slurry to two-season Zizania aquatica Turcz. growth. The potential factors that restrict the rational use of biogas slurry were also clarified. Mineral N fertilizer can be completely or partly substituted by N fertilizer from biogas slurry to satisfy Z. aquatica plant growth. It was not at the cost of sacrificing yield, dry matter accumulation, N accumulation and physiological N use efficiency in the above-ground parts. However, the growth inhibition occurs when the N quantity in biogas slurry was 2 or 2.7 times higher than that of mineral N fertilizer. Vitamin C in non-shell swollen culms (as edible part) of Z. aquatica significantly increased after biogas slurry application. Biogas slurry application substantially increased the N concentrations, i.e., total N, NH₄ ⁺–N, and NO₃ ^?–N in floodwater and delayed the time to reach national discharge standards. However, biogas slurry application did not affect the N concentrations in percolating water compared with the treatment with mineral N fertilizer only. Applying biogass slurry did not generate potential pollution risks by trace elements (Cu, Zn, Pb, Cr, Cd, As, and Hg) in the non-shell swollen culm and soil, and did not increase the nitrate content in non-shell swollen culm. We found the NH₄ ⁺–N concentration in biogas slurry can account for 77–93% of total N and reflects the N level in biogas slurry to a great degree. Semi-quantitative color-based colorimetric methods possessing simple and fast characteristics should be developed to determine the NH₄ ⁺–N concentration with the purpose of promoting reasonable use of biogas slurry in area of crop cultivation. Otherwise, excessive use of biogas slurry can adversely affect crops and increase environmental risks.     

Survival of human derived Lactobacillus plantarum in fermented cereal extracts during refrigerated storage

The aim of this study was to investigate the survival of a potentially probiotic Lactobacillus plantarum strain in barley, wheat and barley malt extracts. The extracts were produced from three flour/water suspensions, i.e., 5%, 20%, 30% w/w. After inoculation, the cultures were incubated for 24 h at 37 °C, and were subsequently stored at 4 °C for up to seventy days. The lactic acid and reducing sugar concentrations at the beginning of storage were significantly different between the fermented media, ranging from 0.5 g/L to 17 g/L and from 0.8 g/L to 6.5 g/L respectively, while the pH ranged between 2.9 and 3.4. It was observed that the cells survived much better in the malt extracts compared to barley and wheat extracts during refrigerated storage. Based on the results from a study using model media and supplemented cereal extracts it was derived that this was most likely due to their higher sugar concentration and the presence of protective unidentified compounds, albeit the fact that the malt extracts contained higher amounts of lactic acid.     

SIMULATION OF A TWO PHASE FLOW BY CFD: ANALYSIS OF THE COMPUTATIONAL METHOD

When using a Computational Fluid Dynamics (CFD) code for the simulation of a two phase system, special attention must be given to the solution procedure. Fluid dynamics in CFD codes are obtained by iterative computations, and criteria must be established to decide the number of iterations needed to obtain a convergent solution under certain defined conditions. In this work, the predicted liquid and gas flow patterns obtained in the simulation of hydrodynamics in bubble columns are analysed throughout the computational process, and the effects of some parameters affecting the computation are studied (dimension of the grid, working conditions, scale-up, relaxation used in the calculations, free surface performance). It was found that each of these parameters affects considerably the solution procedure (though in a different manner) and therefore no general criteria can be established to decide the number of sweeps necessary for a certain simulation. It is concluded that every simulation should be analysed individually each time the conditions are changed. This analysis clearly helps to understand the reliability of CFD predictions in complex systems.     

Decolouration and lipid oxidation changes of vacuum-packed Iberian dry-cured loin treated with E-beam irradiation (5 kGy and 10 kGy) during refrigerated storage

The effect of irradiation (0, 5 and 10 kGy) on the oxidative and colour stability of vacuum-packed Iberian dry-cured loin slices from pigs fed on concentrate feed (CON) or free-range reared (FRG) stored under refrigerated storage was studied. Irradiation treatment increased lipid oxidation, measured as TBA-RS values and hexanal content of dry-cured loins. It also increased redness (CIE a) and lightness (CIE L) of dry-cured loins. Refrigerated storage reduced the differences due to irradiation treatment of instrumental colour values like lightness. However, the decrease of redness during storage was more marked in irradiated than in non-irradiated dry-cured loin. Storage increased differences in TBA-RS values between irradiated and non-irradiated FRG dry-cured loin, while the opposite trend was found for CON dry-cured loins. In addition, no differences in the hexanal content were found after 30 days of refrigerated storage. Therefore, the storage of Iberian dry-cured loin in absence of oxygen by using a vacuum packaging could be an adequate method to reduce changes associated to irradiation treatment in Iberian dry-cured loin.

Industrial relevance

Iberian dry-cured loin is a high sensory quality meat product with increasing projection in external markets Irradiation has shown to be an effective method to control pathogen and spoilage microorganisms in meat and meat products. However, e-beam irradiation can promote colour and oxidation changes that could modify their sensory characteristics. The study aimed the evaluation of e-beam irradiation at two levels (5 and 10 kGy) — higher doses than those that could be necessary to control pathogen microorganisms in this kind of product — on colour changes and lipid oxidation at vacuum-packed slices of Iberian dry-cured loin during subsequent extended chilled storage. E-beam treatment induced changes in colour and lipid oxidation in sliced Iberian dry-cured loin immediately after treatment and subsequent refrigerated storage.     

Marsupial morphology of reproduction: South America opossum male model

This study aims to describe the morphology of Didelphis sp. male genital organs (penis, testes, epididymis, ductus deferens, prostate, and bulbourethral gland). Ten male animals were used, eight for macroscopic and light microscopy analysis, and two for scanning electron microscopy. The testes and epididymis showed similarity to other eutherian mammals. The bifid penis showed the urethra ending in the medial region where the bifurcation begins, occurring in each segment extension of the urethral groove until the beginning of the glans. Histologically, the penis consists of a cavernous and spongy body, covered by stratified squamous epithelium with loose connective tissue. The urethra was lined by transitional stratified epithelium. In the prostate, prostatic segments were found consisting of tubular glands in a radial arrangement around the urethra, coated externally by a dense connective tissue associated with a relatively thick layer of smooth muscle arranged in two layers that surround the glandular tissue. The animals had three pairs of bulbourethral glands placed at the membranous and cavernous urethra junction with descending and parallel excretory ducts ending caudally in the urethral lumen. Microsc. Res. Tech. 76:388–397, 2013. © 2013 Wiley Periodicals, Inc.     

Vitamin C content and sensorial properties of dehydrated carrots blanched conventionally or by ultrasound

Vitamin C content and sensorial properties have been evaluated in air-dried carrots previously subjected to different ultrasound (US) or conventional blanching pretreatments. In addition, mass spectral fingerprints obtained by the Headspace ChemSensor System have been evaluated for the first time for classification of carrots according to their processing. Conventional blanching treatments at high temperature gave rise to carrots with retention of vitamin C in the range 37.5–85%, whereas carrots blanched conventionally at 60 °C and by US-probe at temperatures up to 60 and 70 °C showed vitamin C retention values lower than 4%. Regarding sensorial analysis of rehydrated carrots, US-pretreated samples presented acceptable quality, and no statistically significant differences with respect to conventionally blanched carrots, were detected. In spite of this, differentiation of samples processed under comparable intensity conditions and/or with similar composition was possible from their mass spectral fingerprints after chemometric data analysis.     

An Experimental Technique for the Analysis of Slug Flows in Pneumatic Pipelines Using Pressure Measurements

An experimental technique has been developed to measure the flow characteristics of slugs in dense phase pneumatic conveying using pressure measurements. This method is based on the unique characteristics of slug flows in pipes, i.e., an axial pressure fluctuation along the pipeline and a pressure difference in the radial direction at the back of a slug. Standard differential pressure transducers were used in this study and the influence of the finite response time of these transducers was considered. Experiments were conducted over a range of gas-solids flow conditions and experimental data were analyzed to describe the behavior of solids slugs through pipes. The calculated slug velocity and length using axial pressure measurements were confirmed by video recordings, and the synthesis between axial and radial pressure signals showed reasonable agreement in flow pattern analysis. This relatively simple measuring technique has been found effective in detecting solids slugs traveling through horizontal pipes and will distinguish various flow regimes. It provides a useful and easily applied tool for system optimizing and benchmarking in industrial applications.     

Checkpoint Kinase 1 Pharmacological Inhibition Synergizes with DNA-Damaging Agents and Overcomes Platinum Resistance in Basal-Like Breast Cancer

Basal-like breast cancer is an incurable disease with limited therapeutic options, mainly due to the frequent development of anti-cancer drug resistance. Therefore, identification of druggable targets to improve current therapies and overcome these resistances is a major goal. Targeting DNA repair mechanisms has reached the clinical setting and several strategies, like the inhibition of the CHK1 kinase, are currently in clinical development. Here, using a panel of basal-like cancer cell lines, we explored the synergistic interactions of CHK1 inhibitors (rabusertib and SAR020106) with approved therapies in breast cancer and evaluated their potential to overcome resistance. We identified a synergistic action of these inhibitors with agents that produce DNA damage, like platinum compounds, gemcitabine, and the PARP inhibitor olaparib. Our results demonstrated that the combination of rabusertib with these chemotherapies also has a synergistic impact on tumor initiation, invasion capabilities, and apoptosis in vitro. We also revealed a biochemical effect on DNA damage and caspase-dependent apoptosis pathways through the phosphorylation of H2AX, the degradation of full-length PARP, and the increase of caspases 3 and 8 activity. This agent also demonstrated synergistic activity in a platinum-resistant cell line, inducing an increase in cell death in response to cisplatin only when combined with rabusertib, while no toxic effect was found on non-tumorigenic breast tissue-derived cell lines. Lastly, the combination of CHK1 inhibitor with cisplatin and gemcitabine resulted in more activity than single or double combinations, leading to a higher apoptotic effect. In conclusion, in our study we identify therapeutic options for the clinical development of CHK1 inhibitors, and confirm that the inhibition of this kinase can overcome acquired resistance to cisplatin.