Biochar and compost increase crop yields but the effect is short term on sandplain soils of Western Australia

Sandplain soils on the south coast of Western Australia have low inherent fertility, which is mainly due to poor nutrient retention caused by insufficient clay and organic colloidal material. Previous research has shown the benefits in nutrient levels and retention from adding clay to sandplain soils; however, there is almost no information on the addition of organic amendments. A field experiment was established at the Esperance Downs Research Station, Western Australian, in May 2010, to assess the effects of wheat straw (WS) and chicken manure (CM) biochars and compost with and without phosphorus (P) addition on soil properties and crop production over five growing seasons. The five seasons alternated between winter and summer crops. The CM and WS biochar and compost treatments significantly increased crop yields and P uptake in 3, 2 and 1 of the five seasons, respectively. The yield increases (. P < 0.05) were no more than 8%. By the end of the third season, no differences in crop yields were found that could be attributed to the organic amendments. The addition of P increased crop yields in each winter cropping season. Phosphorus addition explained more than 30% of the variation in crop yields. Despite marginal P levels and summer drought conditions, arbuscular mycorrhizal root colonisation was not affected by the organic amendments. There were no significant interactions between the organic amendments and P addition in terms of crop yields, P uptake or P uptake efficiency. We conclude that much of the effect of the organic amendments was due to direct nutrient addition which dissipated over time

Preconditioning of the tumor microenvironment with oncolytic reovirus converts CD3-bispecific antibody treatment into effective immunotherapy

Background T-cell-engaging CD3-bispecific antibodies (CD3-bsAbs) are promising modalities for cancer immunotherapy. Although this therapy has reached clinical practice for hematological malignancies, the absence of sufficient infiltrating T cells is a major barrier for efficacy in solid tumors. In this study, we exploited oncolytic reovirus as a strategy to enhance the efficacy of CD3-bsAbs in immune-silent solid tumors. Methods The mutant p53 and K-ras induced murine pancreatic cancer model KPC3 resembles human pancreatic ductal adenocarcinomas with a desmoplastic tumor microenvironment, low T-cell density and resistance to immunotherapy. Immune-competent KPC3 tumorbearing mice were intratumorally injected with reovirus type 3 Dearing strain and the reovirus-induced changes in the tumor microenvironment and spleen were analyzed over time by NanoString analysis, quantitative RT-PCR and multicolor flow cytometry. The efficacy of reovirus in combination with systemically injected CD3-bsAbs was evaluated in immune-competent mice with established KPC3 or B16.F10 tumors, and in the close-to-patient human epidermal growth factor receptor 2 (HER2)+ breast cancer model BT474 engrafted in immunocompromised mice with human T cells as effector cells. Results Replication-competent reovirus induced an early interferon signature, followed by a strong influx of natural killer cells and CD8+ T cells, at the cost of FoxP3+ Tregs. Viral replication declined after 7 da

Intertumoral differences dictate the outcome of TGF-β blockade on the efficacy of viro-immunotherapy

The absence of T cells in the tumor microenvironment of solid tumors is a major barrier to cancer immunotherapy efficacy. Oncolytic viruses, including reovirus type 3 Dearing (Reo), can recruit CD8+ T cells to the tumor and thereby enhance the efficacy of immunotherapeutic strategies that depend on high T-cell density, such as CD3-bispecific antibody (bsAb) therapy. TGF-β signaling might represent another barrier to effective Reo&CD3-bsAb therapy due to its immunoinhibitory characteristics. Here, we investigated the effect of TGF-β blockade on the antitumor efficacy of Reo&CD3-bsAb therapy in the preclinical pancreatic KPC3 and colon MC38 tumor models, where TGF-β signaling is active. TGF-β blockade impaired tumor growth in both KPC3 and MC38 tumors. Furthermore, TGF-β blockade did not affect reovirus replication in both models and significantly enhanced the Reo-induced T-cell influx in MC38 colon tumors. Reo administration decreased TGF-β signaling in MC38 tumors but instead increased TGF-β activity in KPC3 tumors, resulting in the accumulation of α-smooth muscle actin (αSMA+) fibroblasts. In KPC3 tumors, TGF-β blockade antagonized the antitumor effect of Reo&CD3-bsAb therapy, even though T-cell influx and activity were not impaired. Moreover, genetic loss of TGF-β signaling in CD8+ T cells had no effect on therapeutic responses. In contrast, TGF-β blockade significantly improved therapeutic efficacy of Reo&CD3-bsAb in mice bearing MC38 colon tumors, resulting in a 100% complete response. Further understanding of the factors that determine this intertumor dichotomy is required before TGF-β inhibition can be exploited as part of viroimmunotherapeutic combination strategies to improve their clinical benefit.Significance:Blockade of the pleiotropic molecule TGF-β can both improve and impair the efficacy of viro-immunotherapy, depending on the tumor model. While TGF-β blockade antagonized Reo&CD3-bsAb combination therapy in the KPC3 model for pancreatic cancer, it resulted in 100% complete responses in the MC38 colon model. Understanding factors underlying this contrast is required to guide therapeutic application.Cancer Signaling networks and Molecular Therapeutic

Neutralizing antibodies impair the oncolytic efficacy of reovirus but permit effective combination with T cell-based immunotherapies

Reovirus type 3 Dearing (Reo), manufactured for clinical application as pelareorep, is an attractive anticancer agent under evaluation in multiple phase 2 clinical trials for the treatment of solid tumors. It elicits its anticancer efficacy by inducing both oncolysis and intratumoral T-cell influx. Because most people have been preexposed to Reo, neutralizing antibodies (NAb) are prevalent in patients with cancer and might present a barrier to effective Reo therapy. Here, we tested serum of patients with cancer and healthy controls (n = 100) and confirmed that Reo NAbs are present in >80% of individuals. To investigate the effect of NAbs on both the oncolytic and the immunostimulatory efficacy of Reo, we established an experimental mouse model with Reo preexposure. The presence of preexposure-induced NAbs reduced Reo tumor infection and prevented Reo-mediated control of tumor growth after intratumoral Reo administration. In B cell–deficient mice, the lack of NAbs provided enhanced tumor growth control after Reo monotherapy, indicating that NAbs limit the oncolytic capacity of Reo. In immunocompetent mice, intratumoral T-cell influx was not affected by the presence of preexposure-induced NAbs and consequently, combinatorial immunotherapy strategies comprising Reo and T-cell engagers or checkpoint inhibitors remained effective in these settings, also after a clinically applied regimen of multiple intravenous pelareorep administrations. Altogether, our data indicate that NAbs hamper the oncolytic efficacy of Reo, but not its immunotherapeutic capacity. Given the high prevalence of seropositivity for Reo in patients with cancer, our data strongly advocate for the application of Reo as part of T cell–based immunotherapeutic strategies. Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Soil management systems to overcome multiple constraints for dryland crops on deep sands in a water limited environment on the south coast of Western Australia

Deep sands on the south coast sandplain of Western Australia (WA) have multiple soil constraints including water repellence, high soil strength, low nutrient levels and subsoil acidity. The aim of the study was to test contrasting methods of managing water repellence and to assess their impacts on one or more soil constraints to crop production. These methods included seeding tyne design (knife point, winged points, paired row), soil wetting agent addition, strategic inversion tillage (rotary spading, mouldboard ploughing to 0.35 m) and clay-rich subsoil addition (170 t ha−1 with incorporation by spading to 0.20 or 0.35 m). Limesand (2 t ha−1) was applied as a split plot treatment prior to tillage. Cumulative crop yields were increased by 2.1–2.6 t ha−1 over five years by the strategic deep tillage and clay application treatments compared to the control. Water repellence was reduced by the inversion ploughing and subsoil clay addition treatments only. The effect of water repellence on crop establishment was expressed only in low rainfall years (Decile < 4) and mitigated by the paired row, wetting agent, spader and clay-amended treatments. In all years, plant numbers were adequate to achieve yield potential regardless of treatment. Soil K and plant tissue K and B were increased where clay had been applied. Inversion tillage reduced soil pH, organic carbon (OC) and macro nutrients in the 0–0.1 m layer although in most years there was no significant decline in plant tissue macro nutrient levels. Soil strength was reduced as a result of the inversion tillage to a depth of 0.35 m. However, the alleviation of soil strength and the crop yield responses diminished with time due to re-compaction. No crop response to the applied lime was found over five years at this site since the soil pHCaCl2 exceeded 4.7 within the root zone. In terms of soil constraints, we conclude that compaction was the dominant constraint at this site followed by water repellence and K deficiency

Arming oncolytic reovirus with GM-CSF gene to enhance immunity

Therapeutic cell differentiatio

Thermal effects in singly resonant continuous-wave optical parametric oscillators

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