Re-conceptualizing scale boundaries: The case of Dutch helemaal

Maximizers – adverbs denoting a maximum degree of a property (e.g. completely) – are often re-conceptualized as boosters denoting a high degree (cf. very). As a result, these degree adverbs come to modify unbounded adjectives which are not compatible with the idea of a maximum value. Although this kind of meaning change proved cross-linguistically robust, the exact mechanisms of this process have never been investigated. The present paper aims to shed more light onto semantic and contextual factors facilitat-ing combinations of open-scale (unbounded) adjectives with closed-scale (bounded) adverbs by analyzing the distribution of the Dutch maximizer helemaal in the Corpus of Spoken Dutch. Following the boundedness hypothesis, we hypothesized that configura-tional harmony destroyed by combinations of the maximizer helemaal with unbounded adjectives can be restored by either imposing scale boundaries onto, by default, un-bounded adjectival scales, or by re-conceptualizing the degree adverb as an unbounded modifier. Both predictions were confirmed by the data in this study. The findings sug-gest that there is no one-to-one relationship between semantic classes of adjectives and scalar structures associated with them. Rather, scalar meanings are a matter of dynamic construal constrained by semantic properties of adjectives and degree modifiers, as well as by context and world knowledge

Photocatalytic treatment of diverse contaminants of potential concern in oil sands process-affected water

Oil sands process-affected water (OSPW), generated by surface mining in Canada’s oil sands, require treatment of environmentally persistent dissolved organic compounds before release to the watershed. Conventional chemical and mechanical treatments have not proved suitable for treating the large quantities of stored OSPW, and the biological recalcitrance of some dissolved organics may not be adequately addressed by conventional passive treatment systems. Previous work has evaluated photocatalytic treatment as a passive advanced oxidation process (P-AOP) for OSPW remediation. This work expands upon this prior research to further characterize the effects of water chemistry on the treatment rate and detoxification threshold. Under artificial sunlight, buoyant photocatalysts (BPCs) detoxified all OSPW samples within 1 week of treatment time with simultaneous treatment of polycyclic aromatic hydrocarbons, naphthenic acid fraction components (NAFCs), and un-ionized ammonia. Overall, these results further demonstrate passive photocatalysis as an effective method for treatment of OSPW contaminants of potential concern (COPCs)

Hepatitis B virus integrations promote local and distant oncogenic driver alterations in hepatocellular carcinoma

International audienceObjective: Infection by HBV is the main risk factor for hepatocellular carcinoma (HCC) worldwide. HBV directly drives carcinogenesis through integrations in the human genome. This study aimed to precisely characterise HBV integrations, in relation with viral and host genomics and clinical features.Design: A novel pipeline was set up to perform viral capture on tumours and non-tumour liver tissues from a French cohort of 177 patients mainly of European and African origins. Clonality of each integration event was determined with the localisation, orientation and content of the integrated sequence. In three selected tumours, complex integrations were reconstructed using long-read sequencing or Bionano whole genome mapping.Results: Replicating HBV DNA was more frequently detected in non-tumour tissues and associated with a higher number of non-clonal integrations. In HCC, clonal selection of HBV integrations was related to two different mechanisms involved in carcinogenesis. First, integration of viral enhancer nearby a cancer-driver gene may lead to a strong overexpression of oncogenes. Second, we identified frequent chromosome rearrangements at HBV integration sites leading to cancer-driver genes (TERT, TP53, MYC) alterations at distance. Moreover, HBV integrations have direct clinical implications as HCC with a high number of insertions develop in young patients and have a poor prognosis.Conclusion: Deep characterisation of HBV integrations in liver tissues highlights new HBV-associated driver mechanisms involved in hepatocarcinogenesis. HBV integrations have multiple direct oncogenic consequences that remain an important challenge for the follow-up of HBV-infected patients

A light touch: solar photocatalysis detoxifies oil sands process-affected waters prior to significant treatment of naphthenic acids or acid extractable organics

The toxicity of oil sands process-affected water (OSPW) has been associated to its dissolved organics, a complex mixture of naphthenic acid fraction components (NAFCs). Here, we evaluated solar treatment with buoyant photocatalysts (BPCs) as a candidate passive advanced oxidation process (P-AOP) for OSPW remediation, according to both analytical chemistry and standard rainbow trout (Oncorhynchus mykiss) and fathead minnow (Pimephales promelas) whole effluent toxicity (WET) bioassays. Solar photocatalysis with BPCs fully degraded naphthenic acids (NAs) and acid extractable organics (AEO) in 3 different OSPW samples, however fish toxicity was eliminated well before concentrations of dissolved organics had significantly diminished, within <2 days of sunlight exposure for all OSPWs. Classical NAs and AEO, traditionally considered among the principal toxicants in OSPW, were not correlated with OSPW toxicity herein. Instead, petroleomic mass spectrometry (MS) analysis revealed low polarity organosulfur NAFCs – O2S− and OS+ (putatively naphthenic sulfoxides), together composing <10% of the total AEO – were correlated with WET outcomes, and apparently accounted for the majority of waters’ toxicity, as described by a physiologically-based model (PBM) of tissue partitioning. These results demonstrate that complete elimination of OSPW toxicity per standard WET bioassays is achievable without significant changes to overall concentrations of dissolved organics, suggesting that most AEO are toxicologically benign, and toxicity may instead be driven by only a small subset of NAFCs, which are preferentially photocatalytically treated. These findings have implications for OSPW release, for which a less extensive but more selective treatment may be required than previously expected

BAP1 mutations define a specific subgroup of hepatocellular carcinoma with fibrolamellar features and PKA activation Short title: BAP1 HCC have FLC features and activate PKA

International audienceBACKGROUND AND AIMS:DNAJB1-PRKACA fusion is a specific driver event in fibrolamellar carcinoma (FLC), a rare subtype of hepatocellular carcinoma (HCC) occurring in adolescents and young adults. In older patients, molecular determinants of HCC with mixed histological features of HCC and FLC (mixed-FLC/HCC) remain to be discovered.METHODS:A series of 151 liver tumors including 126 HCC, 15 FLC, and 10 mixed-FLC/HCC were analyzed by RNAseq and whole-genome- or whole-exome-sequencing. Western-blots were performed to validate genomics discoveries. Results were validated using the TCGA database.RESULTS:Most of the mixed-FLC/HCC RNAseq clustered in a robust subgroup of 17 tumors all showing mutation or translocation inactivating BAP1 that codes for the BRCA1 associated protein-1. Similar to FLC, BAP1-HCC were significantly enriched in female, tumor fibrosis and the lack of chronic liver disease when compared to non-BAP1-HCC. However, patients were older and with a poorer prognosis than FLC patients. BAP1 tumors were immune hot, showed progenitor features, did not show DNAJB1-PRKACA fusion and were almost all non-mutated for CTNNB1, TP53 and TERT promoter. In contrast, 80% of the BAP1 tumors showed a chromosome gain of PRKACA at 19p13, combined with a loss of PRKAR2A (coding for the inhibitory regulatory subunit of PKA) at 3p21, leading to a high PRKACA/PRKAR2A ratio at the mRNA and protein levels.CONCLUSION:We have characterized a subgroup of BAP1-driven HCC bearing fibrolamellar-like features and a dysregulation of the PKA pathway, which could be at the root of the clinical and histological similarities between BAP1 tumors and DNAJB1-PRKACA FLCs

Adeno-associated virus in the liver: natural history and consequences in tumor development

International audienceOBJECTIVE:Adeno-associated virus (AAV) is a defective mono-stranded DNA virus, endemic in human population (35%-80%). Recurrent clonal AAV2 insertions are associated with the pathogenesis of rare human hepatocellular carcinoma (HCC) developed on normal liver. This study aimed to characterise the natural history of AAV infection in the liver and its consequence in tumour development.DESIGN:Viral DNA was quantified in tumour and non-tumour liver tissues of 1461 patients. Presence of episomal form and viral mRNA expression were analysed using a DNAse/TaqMan-based assay and quantitative RT-PCR. In silico analyses using viral capture data explored viral variants and new clonal insertions.RESULTS:AAV DNA was detected in 21% of the patients, including 8% of the tumour tissues, equally distributed in two major viral subtypes: one similar to AAV2, the other hybrid between AAV2 and AAV13 sequences. Episomal viral forms were found in 4% of the non-tumour tissues, frequently associated with viral RNA expression and human herpesvirus type 6, the candidate natural AAV helper virus. In 30 HCC, clonal AAV insertions were recurrently identified in CCNA2, CCNE1, TERT, TNFSF10, KMT2B and GLI1/INHBE. AAV insertion triggered oncogenic overexpression through multiple mechanisms that differ according to the localisation of the integration site.CONCLUSION:We provided an integrated analysis of the wild-type AAV infection in the liver with the identification of viral genotypes, molecular forms, helper virus relationship and viral integrations. Clonal AAV insertions were positive selected during HCC development on non-cirrhotic liver challenging the notion of AAV as a non-pathogenic virus