No abstract

Intensive development of organometal halide perovskite solar cells has lead to a dramatic surge in power conversion efficiency up to 20%. Unfortunately, the most efficient perovskite solar cells all contain lead (Pb), which is an unsettling flaw that leads to severe environmental concerns and is therefore a stumbling block envisioning their large-scale application. Aiming for the retention of favorable electro-optical properties, tin (Sn) has been considered the most likely substitute. Preliminary studies have however shown that Sn-based perovskites are highly unstable and, moreover, Sn is also enlisted as a harmful chemical, with similar concerns regarding environment and health. To bring more clarity into the appropriateness of both metals in perovskite solar cells, we provide a case study with systematic comparison regarding the environmental impact of Pb- and Sn-based perovskites, using zebrafish (Danio Rerio) as model organism. Uncovering an unexpected route of intoxication in the form of acidification, it is shown that Sn based perovskite may not be the ideal Pb surrogate.

Progesterone (PRE) or glucocorticoid receptor (GRE) DNA binding sites are often found clustered with binding sites for other transcription factors. Individual protein binding sites were tested without the influence of adjacent factors by analyzing isolated combinations of several transcription factor binding sites with PREs or GREs. All show strong synergistic effects on steroid induction. The degree of synergism is inversely related to the strength of the GRE. Thus, a steroid responsive unit can be composed of several modules that, if positioned correctly, act synergistically.

Glucocorticoid receptor binding sites (GRE) are often tightly clustered with other transcription factor binding sequences. Examples of this occur upstream of the genes for chicken lysozyme and human metallothionein IIA (ref. 3), in several retroviral LTRs and upstream of the rat tryptophan oxygenase (TO) gene. In the TO gene, sequences immediately upstream of a glucocorticoid receptor binding site are required for steroid induction and contain a CACCC-box identical to that found in the beta globin gene. Here we demonstrate specific binding to this TO-CACCC element and show that it will also act cooperatively with a MMTV glucocorticoid receptor binding site. The response to dexamethasone is independent of the order and relative orientation of these elements but does depend on their precise spacing. Optimal induction occurs at a periodicity of approximately 10 base pairs (bp) indicating a requirement for stereospecific alignment. Binding to the CACCC box, however, is not affected by its distance from the glucocorticoid receptor site. We conclude that the observed cooperativity is mediated by protein:protein interactions and does not depend on cooperative DNA binding.

Overexpression and inhibitor studies have suggested that the c-Myc target gene for ornithine decarboxylase (ODC), the enzyme which converts ornithine to putrescine, plays an important role in diverse biological processes, including cell growth, differentiation, transformation, and apoptosis. To explore the physiological function of ODC in mammalian development, we generated mice harboring a disrupted ODC gene. ODC-heterozygous mice were viable, normal, and fertile. Although zygotic ODC is expressed throughout the embryo prior to implantation, loss of ODC did not block normal development to the blastocyst stage. Embryonic day E3.5 ODCdeficient embryos were capable of uterine implantation and induced maternal decidualization yet failed to develop substantially thereafter. Surprisingly, analysis of ODC-deficient blastocysts suggests that loss of ODC does not affect cell growth per se but rather is required for survival of the pluripotent cells of the inner cell mass. Therefore, ODC plays an essential role in murine development, and proper homeostasis of polyamine pools appears to be required for cell survival prior to gastrulation.Overexpression of the c-Myc, N-Myc, or L-Myc members of the Myc oncogene family is a common event in human tumors. This selection likely reflects Myc's ability to provide continuous proliferative and angiogenic signals under growth-limiting conditions, such as those that occur in the tumor microenvironment (38). However, Myc's propensity to induce continuous proliferation also blocks terminal differentiation (11) and triggers the apoptotic program (2). c-Myc is a basic helix-loophelix leucine zipper protein that exhibits sequence-specific DNA binding to CACGTG or CACATG elements when dimerized with its obligate basic helix-loop-helix leucine zipper partner Max (8). Despite Myc's well-defined function as a transcriptional transactivator, the numbers of its ascribed targets that have been proven to be direct are relatively few, but they do include ornithine decarboxylase (ODC) (6), ␣-prothymosin (15), eIF-4E (44), carbamoyl-phosphate synthase-aspartate carbamoyltransferase-dihydroorotase (cad) (28), a DEAD box-related gene (MrDb) (20), the ubiquitin E2 ligase Cul1 (32), and ECA39 (7). A compelling example of a target gene that contributes to c-Myc's biological effects is ODC (34, 35), which is activated by growth factors and by c-Myc through two conserved CACGTG sites present in the first intron of vertebrate ODC genes (6). ODC is the key regulator of the polyamine biosynthetic pathway and decarboxylates L-ornithine to form putrescine (50). ODC expression is highly regulated by changes in its transcription, translation, and RNA and protein half-life (40). Furthermore, ODC enzyme activity is tightly controlled and shows biphasic induction during late G 1 and at G 2 /M (5). Inhibition of ODC by difluoromethylornithine (DFMO) compromises cell growth and transformation (3) and induces cell cycle arrest in G 1 (35,43). ODC inhibition results in marked reductions in the intracellular levels of th...