Application of Absorption and Scattering Properties Obtained through Image Pre-Classification Method Using a Laser Backscattering Imaging System to Detect Kiwifruit Chilling Injury

Kiwifruit chilling injury (CI) damage occurs after long-term exposure to low temperature. A non-destructive approach to detect CI injury was tested in the present study, using a laser backscattering image (LBI) technique calibrated with 56 liquid phantoms for providing absorption coefficient (µa) and reduced scattering coefficient (µs’). Calibration of LBI resulted in a true-positive (TP) classification of 91.5% and 65.6% of predicted µs’ and µa, respectively. The optical properties of ‘SunGold™’and ‘Hayward’ kiwifruit were analysed at 520 nm with a two-step protocol capturing pre-classification according to the LBI parameters used in the calibration and estimation with the Farrell equation. Severely injured kiwifruit showed white corky tissue and water soaking, reduced soluble solids content and firmness measured destructively. Non-destructive classification results for ‘SunGold™’ showed a high percentage of TP for severe CI of 92% and 75% using LBI parameters directly and predicted µa and µs’ after pre-classification, respectively. The classification accuracy for severe CI ‘Hayward’ kiwifruit with LBI parameter was low (58%) and with µa and µs’ decreased further (35%), which was assumed to be due to interference caused by the long trichomes on the fruit surface

Yttrium-90 Radioembolization in Patients with Hepatocellular Carcinoma Who have Previously Received Sorafenib

Purpose: Yttrium-90 radioembolization (RE) is a locoregional therapy option for hepatocellular carcinoma (HCC). Sorafenib is a multikinase inhibitor used in HCC that can potentially affect the efficacy of RE by altering tumor vascularity or suppressing post-irradiation angiogenesis. The safety and efficacy of sorafenib followed by RE has not been previously reported. Materials and Methods: Patients with HCC who received RE after sorafenib were included in this retrospective review. Overall survival, toxicity, and maximal radiographic response and necrosis criteria were examined. Results: Ten patients (15 RE administrations) fit the inclusion criteria. All were Barcelona Clinic Liver Cancer (BCLC) stage C. Median follow-up was 16.5 weeks. Median overall survival and radiographic progression-free survival were 30 and 28 weeks, respectively. Significant differences in overall survival were seen based on Child-Pugh class (p = 0.002) and radiographic response (p = 0.009). Three patients had partial response, six had stable disease, and one had progressive disease. Grade 1 or 2 acute fatigue, anorexia, and abdominal pain were common. Three patients had Grade 3 ascites in the setting of disease progression. Two patients had Grade 3 biochemical toxicity. One patient was sufficiently downstaged following RE and sorafenib to receive a partial hepatectomy. Conclusion: Yttrium-90 RE in patients with HCC who have received sorafenib demonstrate acceptable toxicity and rates of radiographic response. However, the overall survival is lower than that reported in the literature on RE alone or sorafenib alone. This may be due in part to more patients in this study having advanced disease compared to these other study populations. Larger prospective studies are needed to determine whether the combination of RE and sorafenib is superior to either therapy alone

The Deep Sea and Me : using a science center exhibit to promote lasting public literacy and elucidate public perception of the deep sea

A critical barrier to effective management of deep-sea resources is a lack of understanding by society of the benefits received from the oceans. To address this knowledge gap, we applied an iterative design-based research methodology to evaluate (1) how to effectively use an exhibit to increase public literacy of the deep sea over the short and long-term and (2) how visitors to a public science center perceive the deep sea. Using observations of visitor interactions and surveys of visitors, we evaluated three iterations of an exhibit that highlighted deep-sea ecosystem services and habitats as a case study of exhibit efficacy. Exhibits containing video and interactive components were effective in communicating deep-sea information that was retained by visitors over the long-term. For many visitors, the exhibit was their first introduction to the deep sea. Visitors agreed it is important to learn about the deep sea and expressed interest in learning more about deep-sea animals, habitats, resources, and benefits to humans. Visitors tended to agree with protection-oriented value statements and disagree with use-oriented value statements toward the deep sea. This study provides insight into how to effectively communicate policy-relevant information about the deep sea to an audience that has little to no prior knowledge of the ecosystem, yet who will be increasingly responsible for making use decisions of this habitat

Conceptualizing Ecological Responses to Dam Removal: If You Remove It, What’s to Come?

One of the desired outcomes of dam decommissioning and removal is the recovery of aquatic and riparian ecosystems. To investigate this common objective, we synthesized information from empirical studies and ecological theory into conceptual models that depict key physical and biological links driving ecological responses to removing dams. We define models for three distinct spatial domains: upstream of the former reservoir, within the reservoir, and downstream of the removed dam. Emerging from these models are response trajectories that clarify potential pathways of ecological transitions in each domain. We illustrate that the responses are controlled by multiple causal pathways and feedback loops among physical and biological components of the ecosystem, creating recovery trajectories that are dynamic and nonlinear. In most cases, short-term effects are typically followed by longer-term responses that bring ecosystems to new and frequently predictable ecological condition, which may or may not be similar to what existed prior to impoundment

Hurricane Effects on a Shallow Lake Ecosystem and Its Response to a Controlled Manipulation of Water Level

In order to reverse the damage to aquatic plant communities caused by multiple years of high water levels in Lake Okeechobee, Florida (U.S.), the Governing Board of the South Florida Water Management District (SFWMD) authorized a "managed recession" to substantially lower the surface elevation of the lake in spring 2000. The operation was intended to achieve lower water levels for at least 8 weeks during the summer growing season, and was predicted to result in a large-scale recovery of submerged vascular plants. We treated this operation as a whole ecosystem experiment, and assessed ecological responses using data from an existing network of water quality and submerged plant monitoring sites. As a result of large-scale discharges of water from the lake, coupled with losses to evaporation and to water supply deliveries to agriculture and other regional users, the lake surface elevation receded by approximately 1 m between April and June. Water depths in shoreline areas that historically supported submerged plant communities declined from near 1.5 m to below 0.5 m. Low water levels persisted for the entire summer. Despite shallow depths, the initial response (in June 2000) of submerged plants was very limited and water remained highly turbid (due at first to abiotic seston and later to phytoplankton blooms). Turbidity decreased in July and the biomass of plants increased. However, submerged plant biomass did not exceed levels observed during summer 1999 (when water depths were greater) until August. Furthermore, a vascular plant-dominated assemblage (Vallisnera, Potamogeton, and Hydrilla) that occurred in 1999 was replaced with a community of nearly 98% Chara spp. (a macro-alga) in 2000. Hence, the lake’s submerged plant community appeared to revert to an earlier successional stage despite what appeared to be better conditions for growth. To explain this unexpected response, we evaluated the impacts that Hurricane Irene may have had on the lake in the previous autumn. In mid-October 1999, this category 1 hurricane passed just to the south of the lake, with wind velocities over the lake surface reaching 90 km h-1 at their peak. Output from a three-dimensional hydrodynamic / sediment transport model indicates that during the storm, current velocities in surface waters of the lake increased from near 5 cm s-1 to as high as 100 cm s-1. These strong velocities were associated with large-scale uplifting and horizontal transport of fine-grained sediments from the lake bottom. Water quality data collected after the storm confirmed that the hurricane resulted in lake-wide nutrient and suspended solids concentrations far in excess of those previously documented for a 10-year data set. These conditions persisted through the winter months and may have negatively impacted plants that remained in the lake at the end of the 1999 growing season. The results demonstrate that in shallow lakes, unpredictable external forces, such as hurricanes, can play a major role in ecosystem dynamics. In regions where these events are common (e.g., the tropics and subtropics), consideration should be given to how they might affect long-term lake management programs

Aberrant epithelial GREM1 expression initiates colonic tumorigenesis from cells outside the stem cell niche

Hereditary mixed polyposis syndrome (HMPS) is characterized by the development of mixed-morphology colorectal tumors and is caused by a 40-kb genetic duplication that results in aberrant epithelial expression of the gene encoding mesenchymal bone morphogenetic protein antagonist, GREM1. Here we use HMPS tissue and a mouse model of the disease to show that epithelial GREM1 disrupts homeostatic intestinal morphogen gradients, altering cell fate that is normally determined by position along the vertical epithelial axis. This promotes the persistence and/or reacquisition of stem cell properties in Lgr5-negative progenitor cells that have exited the stem cell niche. These cells form ectopic crypts, proliferate, accumulate somatic mutations and can initiate intestinal neoplasia, indicating that the crypt base stem cell is not the sole cell of origin of colorectal cancer. Furthermore, we show that epithelial expression of GREM1 also occurs in traditional serrated adenomas, sporadic premalignant lesions with a hitherto unknown pathogenesis, and these lesions can be considered the sporadic equivalents of HMPS polyps

Mitochondrial Protease ClpP is a Target for the Anticancer Compounds ONC201 and Related Analogues

ONC201 is a first-in-class imipridone molecule currently in clinical trials for the treatment of multiple cancers. Despite enormous clinical potential, the mechanism of action is controversial. To investigate the mechanism of ONC201 and identify compounds with improved potency, we tested a series of novel ONC201 analogues (TR compounds) for effects on cell viability and stress responses in breast and other cancer models. The TR compounds were found to be ∼50-100 times more potent at inhibiting cell proliferation and inducing the integrated stress response protein ATF4 than ONC201. Using immobilized TR compounds, we identified the human mitochondrial caseinolytic protease P (ClpP) as a specific binding protein by mass spectrometry. Affinity chromatography/drug competition assays showed that the TR compounds bound ClpP with ∼10-fold higher affinity compared to ONC201. Importantly, we found that the peptidase activity of recombinant ClpP was strongly activated by ONC201 and the TR compounds in a dose- and time-dependent manner with the TR compounds displaying a ∼10-100 fold increase in potency over ONC201. Finally, siRNA knockdown of ClpP in SUM159 cells reduced the response to ONC201 and the TR compounds, including induction of CHOP, loss of the mitochondrial proteins (TFAM, TUFM), and the cytostatic effects of these compounds. Thus, we report that ClpP directly binds ONC201 and the related TR compounds and is an important biological target for this class of molecules. Moreover, these studies provide, for the first time, a biochemical basis for the difference in efficacy between ONC201 and the TR compounds

Distinctive Patterns of MicroRNA Expression Associated with Karyotype in Acute Myeloid Leukaemia

Acute myeloid leukaemia (AML) is the most common acute leukaemia in adults; however, the genetic aetiology of the disease is not yet fully understood. A quantitative expression profile analysis of 157 mature miRNAs was performed on 100 AML patients representing the spectrum of known karyotypes common in AML. The principle observation reported here is that AMLs bearing a t(15;17) translocation had a distinctive signature throughout the whole set of genes, including the up regulation of a subset of miRNAs located in the human 14q32 imprinted domain. The set included miR-127, miR-154, miR-154*, miR-299, miR-323, miR-368, and miR-370. Furthermore, specific subsets of miRNAs were identified that provided molecular signatures characteristic of the major translocation-mediated gene fusion events in AML. Analysis of variance showed the significant deregulation of 33 miRNAs across the leukaemic set with respect to bone marrow from healthy donors. Fluorescent in situ hybridisation analysis using miRNA-specific locked nucleic acid (LNA) probes on cryopreserved patient cells confirmed the results obtained by real-time PCR. This study, conducted on about a fifth of the miRNAs currently reported in the Sanger database (microrna.sanger.ac.uk), demonstrates the potential for using miRNA expression to sub-classify cancer and suggests a role in the aetiology of leukaemia

Genomic–transcriptomic evolution in lung cancer and metastasis

Intratumour heterogeneity (ITH) fuels lung cancer evolution, which leads to immune evasion and resistance to therapy. Here, using paired whole-exome and RNA sequencing data, we investigate intratumour transcriptomic diversity in 354 non-small cell lung cancer tumours from 347 out of the first 421 patients prospectively recruited into the TRACERx study. Analyses of 947 tumour regions, representing both primary and metastatic disease, alongside 96 tumour-adjacent normal tissue samples implicate the transcriptome as a major source of phenotypic variation. Gene expression levels and ITH relate to patterns of positive and negative selection during tumour evolution. We observe frequent copy number-independent allele-specific expression that is linked to epigenomic dysfunction. Allele-specific expression can also result in genomic–transcriptomic parallel evolution, which converges on cancer gene disruption. We extract signatures of RNA single-base substitutions and link their aetiology to the activity of the RNA-editing enzymes ADAR and APOBEC3A, thereby revealing otherwise undetected ongoing APOBEC activity in tumours. Characterizing the transcriptomes of primary–metastatic tumour pairs, we combine multiple machine-learning approaches that leverage genomic and transcriptomic variables to link metastasis-seeding potential to the evolutionary context of mutations and increased proliferation within primary tumour regions. These results highlight the interplay between the genome and transcriptome in influencing ITH, lung cancer evolution and metastasis