Teaching of Energy Issues: A debate proposal for a GLobal Reorientation

The growing awareness of serious difficulties in the learning of energy issues has produced a great deal of research, most of which is focused on specific conceptual aspects. In our opinion, the difficulties pointed out in the literature are interrelated and connected to other aspects (conceptual as well as procedural and axiological), which are not sufficiently taken into account in previous research. This paper aims to carry out a global analysis in order to avoid the more limited approaches that deal only with individual aspects. From this global analysis we have outlined 24 propositions that are put forward for debate to lay the foundations for a profound reorientation of the teaching of energy topics in upper high school courses, in order to facilitate a better scientific understanding of these topics, avoid many students' misconceptions and enhance awareness of the current situation of planetary emergency

Genetic loci influencing kidney function and chronic kidney disease

Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10 10 to 10 15). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 × 10 5 and P = 3.6 × 10 4, respectively). Our findings provide insight into metabolic, solute and drug-transport pathways underlying susceptibility to chronic kidney disease

Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin with gemtuzumab ozogamicin improves event-free survival in younger patients with newly diagnosed aml and overall survival in patients with npm1 and flt3 mutations

Purpose To determine the optimal induction chemotherapy regimen for younger adults with newly diagnosed AML without known adverse risk cytogenetics. Patients and Methods One thousand thirty-three patients were randomly assigned to intensified (fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin [FLAG-Ida]) or standard (daunorubicin and Ara-C [DA]) induction chemotherapy, with one or two doses of gemtuzumab ozogamicin (GO). The primary end point was overall survival (OS). Results There was no difference in remission rate after two courses between FLAG-Ida + GO and DA + GO (complete remission [CR] + CR with incomplete hematologic recovery 93% v 91%) or in day 60 mortality (4.3% v 4.6%). There was no difference in OS (66% v 63%; P = .41); however, the risk of relapse was lower with FLAG-Ida + GO (24% v 41%; P < .001) and 3-year event-free survival was higher (57% v 45%; P < .001). In patients with an NPM1 mutation (30%), 3-year OS was significantly higher with FLAG-Ida + GO (82% v 64%; P = .005). NPM1 measurable residual disease (MRD) clearance was also greater, with 88% versus 77% becoming MRD-negative in peripheral blood after cycle 2 (P = .02). Three-year OS was also higher in patients with a FLT3 mutation (64% v 54%; P = .047). Fewer transplants were performed in patients receiving FLAG-Ida + GO (238 v 278; P = .02). There was no difference in outcome according to the number of GO doses, although NPM1 MRD clearance was higher with two doses in the DA arm. Patients with core binding factor AML treated with DA and one dose of GO had a 3-year OS of 96% with no survival benefit from FLAG-Ida + GO. Conclusion Overall, FLAG-Ida + GO significantly reduced relapse without improving OS. However, exploratory analyses show that patients with NPM1 and FLT3 mutations had substantial improvements in OS. By contrast, in patients with core binding factor AML, outcomes were excellent with DA + GO with no FLAG-Ida benefit

Regulation of the erythropoietin gene: D.Phil thesis

Erythropoietin (Epo) is a circulating hormone which regulates red blood cell production, and hence oxygen-carrying capacity. Three striking features of Epo gene expression are that it shows high level induction in response to hypoxia, that it is tightly tissue-restricted and that it is deficient in most forms of renal damage. Each of these aspects has been investigated in this thesis. Chapter 3 concerns the hypoxic-sensing system which induces Epo gene expression via an enhancer element in cultured hepatoma cells. Transient transfection was used to examine a range of cell-lines, which did not produce Epo, for the presence of this oxygen-sensing system. It was demonstrated that such a system is widespread in mammalian cells. It is probable that it is involved in regulating the expression of other genes in response to hypoxia. This widespread oxygen-sensing mechanism contrasts with the tightly tissue-restricted expression of the Epo gene. Transgenic experiments described in Chapters 4 and 5 provide data concerning the DNA sequences involved in this tissue specificity. Sequence from the mouse Epo locus was then used to direct expression of a marker protein, SV40 T antigen, to Epo-expressing cells. This led to identification of the Epo-producing cells in the kidney (Chapter 5) and liver (Chapter 6). In both organs a fibroblast-like population expresses the gene; the Ito cells in the liver and the Type 1 interstitial cells in the kidney. In the liver hepatocytes also produce Epo. Further studies of Epo gene expression would be facilitated by the availability of Epo-producing cell lines. SV40 T antigen is a viral oncogene, and expression of this protein was used as a proliferative stimulus in vivo. The effects of this, and attempts to isolate these cells form the subject of Chapter 7. Chapter 7 also describes experiments in which renal injury was combined with visualisation of individual Epo-producing cells. A homologous recombination at the Epo locus resulted in an allele which expressed the hormone at a greatly reduced level. The phenotype of animals homozygous for this allele is described in Chapter 8. Experiments designed to produce further modification of the Epo locus by this method, and to assess its utility in modifying the mouse genome are also described

Re-evaluation of pachycormid fishes from the Late Jurassic of Southwestern Germany

Pachycormidae is an extinct group of Mesozoic fishes that exhibits extensive body size and shape disparity. The Late Jurassic record of the group is dominated by fossils from the lithographic limestone of Bavaria, Germany that, although complete and articulated, are not well characterized anatomically. In addition, stratigraphic and geographical provenance are often only approximately known, making these taxa difficult to place in a global biogeographical context. In contrast, the late Kimmeridgian Nusplingen Plattenkalk of Baden-Württemberg is a well-constrained locality yielding hundreds of exceptionally preserved and prepared vertebrate fossils. Pachycormid fishes are rare, but these finds have the potential to broaden our understanding of anatomical variation within this group, as well as provide new information regarding the trophic complexity of the Nusplingen lagoonal ecosystem. Here, we review the fossil record of Pachycormidae from Nusplingen, including one fragmentary and two relatively complete skulls, a largely complete fish, and a fragment of a caudal fin. These finds can be referred to three taxa: Orthocormus sp., Hypsocormus posterodorsalis sp. nov., and Simocormus macrolepidotus gen. et sp. nov. The latter taxon was erected to replace “Hypsocormus” macrodon, here considered to be a nomen dubium. Hypsocormus posterodorsalis is known only from Nusplingen, and is characterized by teeth lacking apicobasal ridging at the bases, a dorsal fin positioned opposite the anterior edge of the anal fin, and a hypural plate consisting of a fused parhypural and hypurals. The holotype specimen contributes additional palaeobiological information, with small teleosteans preserved as gastric contents and ribs showing signs of callus formation. These new findings extend our knowledge of the anatomy and diversity of Pachycormidae, and represent an important first step in understanding factors controlling their distribution and morphological variation in the Late Jurassic of Europe