La fonction conjonctionnelle de ga-, particule de phrase, dans la stratégie énonciative

Ga- serait l’héritier gotique d’une lointaine particule pronominale de l’indo-européen et serait étymologiquement et fonctionnellement lié au thème *ke/o. Ayant cette lointaine origine pronominale, il garderait le caractère anaphorique et déictique propre à celle-ci. Nous fondons ce que nous appelons la “fonction conjonctionnelle” de ga- sur ces données préliminaires, la logique articulatoire de ga- s’appuyant dès lors sur les fonctions d’anaphore et de cataphore propres aux déictiques. C’est ainsi que nous ne réduisons pas l’incidence de ga- au seul verbe qui la porte, ni non plus sa fonction au seul marquage de l’aspect “perfectif” du verbe. Ces recherches sont fondées sur une analyse de la traduction de la Bible par Wulfila

Multispecies Assessment of Anthropogenic Particle Ingestion in a Marine Protected Area

We have applied a multispecies ecosystem approach to analyse the ingestion of anthropogenic particles (AP) in the gastrointestinal tract of 313 individuals (17 fish species and 8 invertebrate species) from pelagic, demersal and benthic habitats in a marine protected area off the Western Mediterranean (Cabrera National Park). We have quantified and characterized the ingestion at several taxonomic levels of fish, sea urchins, sea cucumbers, bivalves, and jellyfish in relation to biotic/abiotic factors based on taxonomic groups, trophic guilds (functional groups) and habitats. AP ingestion occurrence ranged from 26 to 100% with no significant differences among taxonomic groups. The fish within the MPA showed an overall ingestion occurrence ranging from 0 to 100%, the echinoderms from 29 to 100%, the bivalves from 72 to 96% and the jellyfish 36% ingestion. The ecosystem approach applied to evaluate overall AP ingestion within the species reported that for trophic guilds, the omnivorous species ingested the highest amounts of anthropogenic items, while herbivores ingested significantly fewer items than all other trophic guilds. Moreover, no significant differences were found amongst habitats, indicating a homogeneous spatial distribution of APs at all studied habitats. The multispecies approach provided insight into the high APs exposure to species within Cabrera MPA, highlighting the potential harm linked with marine litter that threatens marine biodiversity.En prensa5,82

Avaluació de l’estat fisiològic del conill (Oryctolagus cuniculus) per mitjà de biomarcadors bioquímics

[cat] El conill europeu (Oryctolagus cuniculus) és una de les espècies de vertebrats més importants dels ecosistemes Mediterranis. L'arribada de malalties virals, com la mixomatosi, han donat lloc a disminucions importants de les poblacions de conills salvatges. La determinació de biomarcadors de l’estat pro-oxidant / anti-oxidant permeten avaluar l’existència d’algun factor ambiental o infecciós que indueixi una situació d’estrès a l’animal. L’objectiu del present estudi va ser avaluar biomarcadors d’estrès a conills obtinguts en diferents modes de captura i en conills afectats per mixomatosi. Els resultats obtinguts no evidencien cap tipus de diferència en les activitats plasmàtiques dels enzims antioxidants, de l’activitat mieloperoxidasa ni dels nivells de malondialdehid en funció de la diferent modalitat de captura: ca eivissenc, fura o grup estabulat. La producció d’espècies reactives per part de les cèl·lules immunitàries tampoc no es veu modificada. Per contra, les activitats dels enzims catalasa, glutatió peroxidasa i glutatió reductasa són significativament més baixes a fetge en animals afectats de mixomatosi respecte als animals sans, mentre que els nivells de malondialdehid són significativament més elevats als animals malalts. En conclusió, el fet que no s’hagin observat diferències derivades del procés de captura ni respecte al grup control, demostra que els conills capturats gaudien d’un bon estat de salut. Els conills afectats per mixomatosi presenten a nivell hepàtic una disminució general de les defenses antioxidants i un augment del dany oxidatiu, cosa que posa de manifest la gravetat de la patologia.[eng] The European rabbit (Oryctolagus cuniculus) is one of the most important vertebrate species in Mediterranean ecosystems. In the last 60 years, the arrival of viral diseases, such as myxomatosis, has led to significant diminution of the populations of wild rabbits. The determination of biomarkers of the pro-oxidant / anti-oxidant status allows the evaluation of the existence of an environmental or infectious factor that induces a situation of stress to the animal and the ability to respond and adapt to this situation. The aim of the present study was to evaluate stress biomarkers from rabbits obtained in different capture modes and rabbits affected by myxomatosis. The results obtained do not show any difference in the plasma activities of antioxidant enzymes, myeloperoxidase activity or malondialdehyde levels depending on the different way of capturing rabbits: Ibizan dogs, ferrets or the confined group. The production of reactive species by immune cells is also unchanged. In contrast, the activities of catalase enzymes, glutathione peroxidase and glutathione reductase are significantly lower in liver in animals affected by myxomatosis compared to healthy animals, while levels of malondialdehyde are significantly higher in diseased animals. In conclusion, the fact that no differences derived from the capture process or the control group have been observed demonstrates that the captured rabbits are in a good state of health. Rabbits affected by myxomatosis have a general decrease in antioxidant defences and an increase in oxidative damage, evidencing the seriousness of the pathology

Impacts of endocrine disrupting chemicals on reproduction in wildlife and humans

Endocrine disrupting chemicals (EDCs) are ubiquitous in aquatic and terrestrial environments. The main objective of this review was to summarize the current knowledge of the impacts of EDCs on reproductive success in wildlife and humans. The examples selected often include a retrospective assessment of the knowledge of reproductive impacts over time to discern how the effects of EDCs have changed over the last several decades. Collectively, the evidence summarized here within reinforce the concept that reproduction in wildlife and humans is negatively impacted by anthropogenic chemicals, with several altering endocrine system function. These observations of chemicals interfering with different aspects of the reproductive endocrine axis are particularly pronounced for aquatic species and are often corroborated by laboratory-based experiments (i.e. fish, amphibians, birds). Noteworthy, many of these same indicators are also observed in epidemiological studies in mammalian wildlife and humans. Given the vast array of reproductive strategies used by animals, it is perhaps not surprising that no single disrupted target is predictive of reproductive effects. Nevertheless, there are some general features of the endocrine control of reproduction, and in particular, the critical role that steroid hormones play in these processes that confer a high degree of susceptibility to environmental chemicals. New research is needed on the implications of chemical exposures during development and the potential for long-term reproductive effects. Future emphasis on field-based observations that can form the basis of more deliberate, extensive, and long-term population level studies to monitor contaminant effects, including adverse effects on the endocrine system, are key to addressing these knowledge gaps

POSEIDON Trial Phase 1b Results: Safety, Efficacy and Circulating Tumor DNA Response of the Beta Isoform-Sparing PI3K Inhibitor Taselisib (GDC-0032) Combined with Tamoxifen in Hormone Receptor Positive Metastatic Breast Cancer Patients.

PURPOSE: The strategy of combining endocrine therapy with PI3K-mTOR inhibition has shown promise in estrogen receptor (ER)-positive breast cancer, but new agents and combinations with a better therapeutic index are urgently needed. Taselisib is a potent, selective, beta-isoform-sparing PI3 kinase inhibitor. PATIENTS AND METHODS: 30 patients with ER-positive, metastatic breast cancer who had failed prior endocrine therapy were treated with escalating doses of taselisib (2 or 4 mg in an intermittent or continuous schedule) combined with tamoxifen 20 mg once daily in this phase 1b study using a "rolling six" design. RESULTS: Taselisib combined with tamoxifen was generally well tolerated, with treatment-emergent adverse events as expected for this class of drugs, including diarrhea (13 patients, 43%), mucositis (10 patients, 33%), and hyperglycemia (8 patients, 27%). No dose-limiting toxicities were observed. Objective responses were seen in 6 of 25 patients with RECIST-measurable disease (ORR 24%). Median time to disease progression was 3.7 months. Twelve of 30 patients (40%) had disease control for 6 months or more. Circulating tumor (ct)DNA studies using next-generation tagged amplicon sequencing identified early indications of treatment response and mechanistically relevant correlates of clinical drug resistance (e.g., mutations in KRAS, ERBB2) in some patients. CONCLUSIONS: Taselisib can be safely combined with tamoxifen at the recommended phase 2 dose of 4 mg given once daily on a continuous schedule. Preliminary evidence of antitumor activity was seen in both PIK3CA mutant and wild-type cancers. The randomized phase 2 part of POSEIDON (testing tamoxifen plus taselisib or placebo) is currently recruiting

Adaptation to flood risk: Results of international paired flood event studies

As flood impacts are increasing in large parts of the world, understanding the primary drivers of changes in risk is essential for effective adaptation. To gain more knowledge on the basis of empirical case studies, we analyze eight paired floods, that is, consecutive flood events that occurred in the same region, with the second flood causing significantly lower damage. These success stories of risk reduction were selected across different socioeconomic and hydro-climatic contexts. The potential of societies to adapt is uncovered by describing triggered societal changes, as well as formal measures and spontaneous processes that reduced flood risk. This novel approach has the potential to build the basis for an international data collection and analysis effort to better understand and attribute changes in risk due to hydrological extremes in the framework of the IAHSs Panta Rhei initiative. Across all case studies, we find that lower damage caused by the second event was mainly due to significant reductions in vulnerability, for example, via raised risk awareness, preparedness, and improvements of organizational emergency management. Thus, vulnerability reduction plays an essential role for successful adaptation. Our work shows that there is a high potential to adapt, but there remains the challenge to stimulate measures that reduce vulnerability and risk in periods in which extreme events do not occur

Assessment of intellectual impairment, health-related quality of life, and behavioral phenotype in patients with neurotransmitter related disorders: data from the iNTD registry

Inherited disorders of neurotransmitter metabolism are a group of rare diseases, which are caused by impaired synthesis, transport or degradation of neurotransmitters or co-factors and result in various degrees of delayed or impaired psychomotor development. To assess the effect of neurotransmitter deficiencies on intelligence, quality of life, and behavior, the data of 148 patients in the registry of the International Working Group on Neurotransmitter Related Disorders (iNTD) was evaluated using results from standardized age-adjusted tests and questionnaires. Patients with a primary disorder of monoamine metabolism had lower IQ scores (mean IQ 58, range 40-100) within the range of cognitive impairment (<70) compared to patients with a BH4 deficiency (mean IQ 84, range 40-129). Short attention span and distractibility were most frequently mentioned by parents, while patients reported most frequently anxiety and distractibility when asked for behavioral traits. In individuals with succinic semialdehyde dehydrogenase deficiency, self-stimulatory behaviors were commonly reported by parents, whereas in patients with dopamine transporter (DAT) deficiency, DNAJC12 deficiency, and monoamine oxidase A deficiency, self-injurious or mutilating behaviors have commonly been observed. Phobic fears were increased in patients with 6-pyruvoyltetrahydropterin synthase deficiency while individuals with sepiapterin reductase deficiency frequently experienced communication and sleep difficulties. Patients with BH4 deficiencies achieved significantly higher quality of life as compared to other groups. This analysis of the iNTD registry data highlights: a) difference in IQ and subdomains of quality of life between BH4 deficiencies and primary neurotransmitter-related disorders, and b) previously underreported behavioral traits

Severity-adjusted evaluation of liver transplantation on health outcomes in urea cycle disorders

Purpose: Liver transplantation (LTx) is performed in individuals with urea cycle disorders when medical management (MM) insufficiently prevents the occurrence of hyperammonemic events. However, there is a paucity of systematic analyses on the effects of LTx on health-related outcome parameters compared to individuals with comparable severity who are medically managed. Methods: We investigated the effects of LTx and MM on validated health-related outcome parameters, including the metabolic disease course, linear growth, and neurocognitive outcomes. Individuals were stratified into “severe” and “attenuated” categories based on the genotype-specific and validated in vitro enzyme activity. Results: LTx enabled metabolic stability by prevention of further hyperammonemic events after transplantation and was associated with a more favorable growth outcome compared with individuals remaining under MM. However, neurocognitive outcome in individuals with LTx did not differ from the medically managed counterparts as reflected by the frequency of motor abnormality and cognitive standard deviation score at last observation. Conclusion: Whereas LTx enabled metabolic stability without further need of protein restriction or nitrogen-scavenging therapy and was associated with a more favorable growth outcome, LTx—as currently performed—was not associated with improved neurocognitive outcomes compared with long-term MM in the investigated urea cycle disorders.</p

Regulation of the Fruit-Specific PEP Carboxylase SlPPC2 Promoter at Early Stages of Tomato Fruit Development

The SlPPC2 phosphoenolpyruvate carboxylase (PEPC; EC 4.1.1.31) gene from tomato (Solanum lycopersicum) is differentially and specifically expressed in expanding tissues of developing tomato fruit. We recently showed that a 1966 bp DNA fragment located upstream of the ATG codon of the SlPPC2 gene (GenBank AJ313434) confers appropriate fruit-specificity in transgenic tomato. In this study, we further investigated the regulation of the SlPPC2 promoter gene by analysing the SlPPC2 cis-regulating region fused to either the firefly luciferase (LUC) or the β-glucuronidase (GUS) reporter gene, using stable genetic transformation and biolistic transient expression assays in the fruit. Biolistic analyses of 5′ SlPPC2 promoter deletions fused to LUC in fruits at the 8th day after anthesis revealed that positive regulatory regions are mostly located in the distal region of the promoter. In addition, a 5′ UTR leader intron present in the 1966 bp fragment contributes to the proper temporal regulation of LUC activity during fruit development. Interestingly, the SlPPC2 promoter responds to hormones (ethylene) and metabolites (sugars) regulating fruit growth and metabolism. When tested by transient expression assays, the chimeric promoter:LUC fusion constructs allowed gene expression in both fruit and leaf, suggesting that integration into the chromatin is required for fruit-specificity. These results clearly demonstrate that SlPPC2 gene is under tight transcriptional regulation in the developing fruit and that its promoter can be employed to drive transgene expression specifically during the cell expansion stage of tomato fruit. Taken together, the SlPPC2 promoter offers great potential as a candidate for driving transgene expression specifically in developing tomato fruit from various tomato cultivars