Muriel Spark, The Prime of Miss Jean Brodie (1961)

Discusses Spark\u27s well-known novel, recognizing its curious amalgamation of acerbic humour, elegance of style, Calvinist spirit, and careful poignancy of plot development, but pointing also to the pleasurable challenge offered by its charismatic protagonist, Jean Brodie, glamorous and romantic, with a proud self-assurance rarely bestowed on female characters, which nonetheless eludes everyone’s emotional grasp

No Incidence of BRAF Mutations in Salivary Gland Carcinomas—Implications for Anti-EGFR Therapies

BRAF is the main effector of KRAS in the RAS-RAF-MAPK axis, a signaling pathway downstream of EGFR. The activation of this cascade is an important pathway in cancer development and is considered a key pathway for therapeutic molecules. Recent studies in metastatic colorectal cancer found that an oncogenic activation of BRAF by a point mutation in exon 15 (V600E) could bypass the EGFR-initiated signaling cascade with the effect that patients bearing the mutant BRAF allele are not likely to benefit from EGFR-targeted therapies. We designed an allele-specific PCR and screened 65 salivary gland carcinoma (SGC) of the main histopathological types for the BRAF V600E mutation. All 65 SGC in this cohort (100%) presented the BRAF wildtype. In a previous study, we found a KRAS wildtype in 98.5% of SGC. These findings imply that SGC rarely acquires mutations that result in a constitutive activation of the signaling cascade downstream of EGFR and this pleads in favor of further therapeutic trials with EGFR-targeting monoclonal antibodies

Volcanic Flank Collapse, Secondary Sediment Failure and Flow‐Transition:Multi‐Stage Landslide Emplacement Offshore Montserrat, Lesser Antilles

Volcanic flank collapses, especially those in island settings, have generated some of the most voluminous mass transport deposits on Earth and can trigger devastating tsunamis. Reliable tsunami hazard assessments for flank collapse‐driven tsunamis require an understanding of the complex emplacement processes involved. The seafloor sequence southeast of Montserrat (Lesser Antilles) is a key site for the study of volcanic flank collapse emplacement processes that span subaerial to submarine environments. Here, we present new 2D and 3D seismic data as well as MeBo drill core data from one of the most extensive mass transport deposits offshore Montserrat, which exemplifies multi‐phase landslide deposition from volcanic islands. The deposits reveal emplacement in multiple stages including two blocky volcanic debris avalanches, secondary seafloor failure and a late‐stage erosive density current that carved channel‐like incisions into the hummocky surface of the deposit about 15 km from the source region. The highly erosive density current potentially originated from downslope‐acceleration of fine‐grained material that was suspended in the water column earlier during the slide. Late‐stage erosive turbidity currents may be a more common process following volcanic sector collapse than has been previously recognized, exerting a potentially important control on the observed deposit morphology as well as on the runout and the overall shape of the deposit

Protein modification with ISG15 blocks coxsackievirus pathology by antiviral and metabolic reprogramming

Protein modification with ISG15 (ISGylation) represents a major type I IFN–induced antimicrobial system. Common mechanisms of action and species-specific aspects of ISGylation, however, are still ill defined and controversial. We used a multiphasic coxsackievirus B3 (CV) infection model with a first wave resulting in hepatic injury of the liver, followed by a second wave culminating in cardiac damage. This study shows that ISGylation sets nonhematopoietic cells into a resistant state, being indispensable for CV control, which is accomplished by synergistic activity of ISG15 on antiviral IFIT1/3 proteins. Concurrent with altered energy demands, ISG15 also adapts liver metabolism during infection. Shotgun proteomics, in combination with metabolic network modeling, revealed that ISG15 increases the oxidative capacity and promotes gluconeogenesis in liver cells. Cells lacking the activity of the ISG15-specific protease USP18 exhibit increased resistance to clinically relevant CV strains, therefore suggesting that stabilizing ISGylation by inhibiting USP18 could be exploited for CV-associated human pathologies

Controlled source electromagnetic measurements offshore the Maltese Islands : implications for offshore freshened groundwater in a carbonate shelf

Carbonate lithologies host considerable quantities of the Earth’s freshwater resources and partially supply a significant amount of the global population with drinkable water. Although they comprise substantial amounts of the coastlines, it is not known if these carbonate lithologies can sustain freshened groundwater offshore, and if this can help meet future water demands in coastal regions. To date, predicting volumes of freshened groundwater within marine carbonates has been challenging. Here, we integrate controlled source electromagnetic profiles with seismic reflection and core log data to derive a lithological model for the eastern carbonate margin of the Maltese Islands, one of the most water-starved countries in the world. Electrical resistivity models are used to guide lithological inference where seismic data provide limited information due to the superimposed seafloor multiple. We show that resistivity values within the Upper Coralline and Globigerina Limestone formations exceed the measured resistivity of seawater-saturated core log samples by at least a factor of four. This could be indicative of offshore freshened groundwater that occupies the pore space of the low permeability limestone along the eastern Maltese shelf. To validate this observation without further ground-truthing data, we use extensive forward modelling to show that a similar resistivity footprint can be achieved by localized interbedded low-porosity or highly cemented units. However, the spatial extent of such units across the entire eastern Maltese margin is geologically improbable. This points to the occurrence of offshore freshened groundwater that was likely emplaced during the last sea-level lowstand.peer-reviewe

Electrical resistivity anomalies offshore a carbonate coastline : evidence for freshened groundwater?

Carbonate lithologies host considerable quantities of the Earth's freshwater resources and partially supply a quarter of the global population with drinkable water. In addition, carbonates constitute substantial amounts of the global coastlines, yet it is not known if and how they can sustain freshened groundwater offshore. Here, we use controlled-source electromagnetic, seismic reflection, and core sample data to derive a lithological model for the eastern margin of the Maltese Islands and identify four distinct resistivity anomalies within the Upper Coralline and Globigerina Limestone formations. The anomalies hosted in the former are likely associated with low porosities, whereas the anomaly within the latter is indicative of pore fluid freshening. Hydrogeological modeling suggests that freshened pore fluids, emplaced during sea-level lowstands and preserved in low permeability units, are potentially still found within carbonate shelves. However, resource potential is low due to its relict nature and low permeability host environment.peer-reviewe

Body weight dissatisfaction and communication with parents among adolescents in 24 countries: international cross-sectional survey

BACKGROUND: Parents have significant influence on behaviors and perceptions surrounding eating, body image and weight in adolescents. The aim of this study was to examine the prevalence of body weight dissatisfaction, difficulty in communication with the parents and the relationship between communication with parents and adolescents' dissatisfaction with their body weight (dieting or perceived need to diet). METHODS: Survey data were collected from adolescents in 24 countries and regions in Europe, Canada, and the USA who participated in the cross-sectional 2001/2002 Health Behaviour of School-Aged Children (HBSC) study. The association between communication with parents and body weight dissatisfaction was examined using binary logistic regression analysis. RESULTS: Body weight dissatisfaction was highly prevalent and more common among girls than boys, among overweight than non-overweight, and among older adolescents than younger adolescents. Difficulty in talking to father was more common than difficulty in talking to mother in all countries and it was greater among girls than among boys and increased with age. Difficulties in talking to father were associated with weight dissatisfaction among both boys and girls in most countries. Difficulties in talking to mother were rarely associated with body weight dissatisfaction among boys while among girls this association was found in most countries. CONCLUSION: The findings suggest that enhanced parent communication might contribute in most countries to less body dissatisfaction in girls and better communication with the father can help avoiding body weight dissatisfaction in boys. Professionals working with adolescents and their families should help adolescents to have a healthy weight and positive body image and promote effective parent – adolescent communication.peerReviewe

European contribution to the study of ROS: A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS).

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.The EU-ROS consortium (COST Action BM1203) was supported by the European Cooperation in Science and Technology (COST). The present overview represents the final Action dissemination summarizing the major achievements of COST Action BM1203 (EU-ROS) as well as research news and personal views of its members. Some authors were also supported by COST Actions BM1005 (ENOG) and BM1307 (PROTEOSTASIS), as well as funding from the European Commission FP7 and H2020 programmes, and several national funding agencies