Microsatellites for the Amazonian Fish Hypophthalmus marginatus

We isolated 41 and characterized 17 microsatellite loci for evaluating the genetic structure of the Amazonian fish Hypophthalmus marginatus, from the Tocantins and Araguaia River in the Eastern Amazonia. Of the 17 selected microsatellite sequences, 15 were dinucleotide repeats, 9 of which were perfect (5–31 repetitions) and 6 were composite motifs. Among these 17 microsatellites, only two were polymorphic. The average number of alleles (Na) observed in the five examined populations ranged from 3.5 to 4.5, while the average observed heterozygosity (Ho) ranged from 0.3 to 0.6. The allelic frequency was less homogeneous at the locus Hm 5 than that for the Hm 13. Genetic diversity was measured in three upstream and two downstream populations under the influence of the Tucuruí Hydroelectric Dam. Our findings provide evidence for low levels of genetic diversity in H. marginatus of the Tocantis basin possibility related to the Dam construction. The Fst and Rst analysis fits well with migratory characteristics of H. marginatus, suggesting the existence of a gene flow mainly in the upstream or downstream directions. To test the hypothesis that the Dam was responsible for the detected reduction on this species genetic diversity, a large number of genetic markers are recommended, covering geographic distribution range of the fish species

Glioblastoma adaptation traced through decline of an IDH1 clonal driver and macro-evolution of a double-minute chromosome

In a glioblastoma tumour with multi-region sequencing before and after recurrence, we find an IDH1 mutation that is clonal in the primary but lost at recurrence. We also describe the evolution of a double-minute chromosome encoding regulators of the PI3K signalling axis that dominates at recurrence, emphasizing the challenges of an evolving and dynamic oncogenic landscape for precision medicin

Parents' Experiences of Receiving the Initial Positive Newborn Screening (NBS) Result for Cystic Fibrosis and Sickle Cell Disease

The clinical advantages of the newborn screening programme (NBS) in the UK are well described in the literature. However, there has been little exploration of the psychosocial impact on the family. This study followed the principles of grounded theory to explore parents' experiences of receiving the initial positive NBS result for their child with cystic fibrosis (CF) or sickle cell disease (SCD). Semi-structured, qualitative interviews were conducted with 22 parents (12 mothers and 10 fathers) whose children had been diagnosed with CF or SCD via NBS and were under the age of 1 year at the time of interview. The main themes that arose from the data were; parents previous knowledge of the condition and the NBS programme, the method of delivery and parental reactions to the result, sharing the results with others, the impact on parental relationships and support strategies. Study conclusions indicate that most parents thought initial positive NBS results should be delivered by a health professional with condition specific knowledge, preferably with both parents present. Genetic counselling needs to include a focus on the impact of NBS results on parental relationships. Careful consideration needs to be given to strategies to support parents of babies who have positive NBS results both in terms of the psychological health and to assist them in sharing the diagnosis

Glioblastoma adaptation traced through decline of an IDH1 clonal driver and macro-evolution of a double-minute chromosome

Background: Glioblastoma (GBM) is the most common malignant brain cancer occurring in adults, and is associated with dismal outcome and few therapeutic options. GBM has been shown to predominantly disrupt three core pathways through somatic aberrations, rendering it ideal for precision medicine approaches. Methods: We describe a 35-year-old female patient with recurrent GBM following surgical removal of the primary tumour, adjuvant treatment with temozolomide and a 3-year disease-free period. Rapid whole-genome sequencing (WGS) of three separate tumour regions at recurrence was carried out and interpreted relative to WGS of two regions of the primary tumour. Results: We found extensive mutational and copy-number heterogeneity within the primary tumour. We identified a TP53 mutation and two focal amplifications involving PDGFRA, KIT and CDK4, on chromosomes 4 and 12. A clonal IDH1 R132H mutation in the primary, a known GBM driver event, was detectable at only very low frequency in the recurrent tumour. After sub-clonal diversification, evidence was found for a whole-genome doubling event and a translocation between the amplified regions of PDGFRA, KIT and CDK4, encoded within a double-minute chromosome also incorporating miR26a-2. The WGS analysis uncovered progressive evolution of the double-minute chromosome converging on the KIT/PDGFRA/PI3K/mTOR axis, superseding the IDH1 mutation in dominance in a mutually exclusive manner at recurrence, consequently the patient was treated with imatinib. Despite rapid sequencing and cancer genome-guided therapy against amplified oncogenes, the disease progressed, and the patient died shortly after. Conclusion: This case sheds light on the dynamic evolution of a GBM tumour, defining the origins of the lethal sub-clone, the macro-evolutionary genomic events dominating the disease at recurrence and the loss of a clonal driver. Even in the era of rapid WGS analysis, cases such as this illustrate the significant hurdles for precision medicine success

Governance and Management Systems in Mediterranean Marine and Coastal Biosphere Reserves

Recent studies in UNESCO World Heritage sites and Biosphere Reserves (BRs) identified gaps regarding the effectiveness of planning, governance, and management. The objective of a study carried out is to develop innovative approaches of evidence-based governance in UNESCO-designated marine protected areas in the Mediterranean Basin. Three different types of Biosphere Reserves have been selected for the present chapter: the Tuscan Islands Archipelago in Italy; the Terres de l'Ebre Delta in Spain; and the marine and coastal area of Gouraya in Algeria. Current and future evidence in the BRs differ and require actions related to the local realities and challenges. The Terres de l'Ebre BR is step by step implementing the new strategies and processes. The Tuscan Island BR has already prepared the frameworks and participatory instruments which await implementation. The Gouraya BR through the National Park established conservation and development functions, but for its realization it still seeks an increase of awareness and commitments of the authorities as well as management tools and funds. The "evidence-based governance and management system" is considered an integrated approach adequately involving the three dimensions top-down, bottom-up, and outside-in. It is an instrument to improve effectiveness of management and to involve the local communities and stakeholders in the decision processes in Biosphere Reserves

Modelling survival : exposure pattern, species sensitivity and uncertainty

The General Unified Threshold model for Survival (GUTS) integrates previously published toxicokinetic-toxicodynamic models and estimates survival with explicitly defined assumptions. Importantly, GUTS accounts for time-variable exposure to the stressor. We performed three studies to test the ability of GUTS to predict survival of aquatic organisms across different pesticide exposure patterns, time scales and species. Firstly, using synthetic data, we identified experimental data requirements which allow for the estimation of all parameters of the GUTS proper model. Secondly, we assessed how well GUTS, calibrated with short-term survival data of Gammarus pulex exposed to four pesticides, can forecast effects of longer-term pulsed exposures. Thirdly, we tested the ability of GUTS to estimate 14-day median effect concentrations of malathion for a range of species and use these estimates to build species sensitivity distributions for different exposure patterns. We find that GUTS adequately predicts survival across exposure patterns that vary over time. When toxicity is assessed for time-variable concentrations species may differ in their responses depending on the exposure profile. This can result in different species sensitivity rankings and safe levels. The interplay of exposure pattern and species sensitivity deserves systematic investigation in order to better understand how organisms respond to stress, including humans