EAPP: Gatekeeper at the crossroad of apoptosis and p21-mediated cell-cycle arrest

We previously identified and characterized E2F-associated phospho-protein (EAPP), a nuclear phosphoprotein that interacts with the activating members of the E2F transcription factor family. EAPP levels are frequently elevated in transformed human cells. To examine the biological relevance of EAPP, we studied its properties in stressed and unstressed cells. Overexpression of EAPP in U2OS cells increased the fraction of G1 cells and lead to heightened resistance against DNA damage- or E2F1-induced apoptosis in a p21-dependent manner. EAPP itself becomes upregulated in confluent cells and after DNA damage and stimulates the expression of p21 independently of p53. It binds to the p21 promoter and seems to be required for the assembly of the transcription initiation complex. RNAi-mediated knockdown of EAPP expression brought about increased sensitivity towards DNA damage and resulted in apoptosis even in the absence of stress. Our results indicate that the level of EAPP is critical for cellular homeostasis. Too much of it results in G1 arrest and resistance to apoptosis, which, paradoxically, might favor cellular transformation. Too little EAPP seems to retard the expression not only of the p21 gene, but also of a number of other genes and ultimately results in apoptosis

Variants of GCKR Affect Both β-Cell and Kidney Function in Patients With Newly Diagnosed Type 2 Diabetes: The Verona Newly Diagnosed Type 2 Diabetes Study 2

In genome-wide association studies, performed mostly in nondiabetic individuals, genetic variability of glucokinase regulatory protein (GCKR) affects type 2 diabetes-relatedphenotypes, kidney function, and risk of chronic kidney disease (CKD). We tested whether GCKR variability affects type 2 diabetes or kidney-related phenotypes in newly diagnosed type 2diabetes. In 509 GAD-negative patients with newly diagnosedtype 2 diabetes,we 1) genotyped six single nucleotide polymorphisms in GCKR genomic region: rs6717980, rs1049817, rs6547626, rs780094, rs2384628, and rs8731; 2) assessedclinical phenotypes, insulin sensitivity by the euglycemic insulin clamp, and b-cell function by state-of-the-art modeling of glucose/C-peptide curves during an oral glucose tolerance test;and 3) estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease formula.The major alleles of rs6717980 and rs2384628 were associated with reduced b-cell function (P<0.05), with mutual additive effects of each variant (P<0.01). The minoralleles of rs1049817 and rs6547626 and the major allele of rs780094 were associated withreduced eGFR according to a recessive model (P<0.03), but with no mutual additive effects of the variants. Additional associations were found between rs780094 and 2-h plasma glucose(P<0.05) and rs8731 and insulin sensitivity (P<0.05) and triglycerides (P<0.05). Our findings are compatible with the idea that GCKR variability may play a pathogenetic role in both type 2 diabetes and CKD. Genotyping GCKR in patients withnewly diagnosed type 2 diabetes might help in identifying patients at high risk for metabolic derangements or CKD

Light-Soaking-Free Inverted Polymer Solar Cells with an Efficiency of 10.5% by Compositional and Surface Modifications to a Low-Temperature-Processed TiO2 Electron-Transport Layer.

Compositional modification and surface treatments of a TiO2 film prepared by a low-temperature route are carried out by a new promising method. Inverted polymer solar cells incorporating the post-treated TiO2 :TOPD electron-transport layer achieve the highest efficiency of 10.5%, and more importantly, eliminate the light-soaking problem that is commonly observed in metal-oxide-based inverted polymer solar cells

Surface passivation effect by fluorine plasma treatment on ZnO for efficiency and lifetime improvement of inverted polymer solar cells

Zinc oxide (ZnO) is an important material for polymer solar cells (PSCs) where the characteristics of the interface can dominate both the efficiency and lifetime of the device. In this work we study the effect of fluorine (SF6) plasma surface treatment of ZnO films on the performance of PSCs with an inverted structure. The interaction between fluorine species present in the SF6 plasma and the ZnO surface is also investigated in detail. We provide fundamental insights into the passivation effect of fluorine by analyzing our experimental results and theoretical calculations and we propose a mechanism according to which a fluorine atom substitutes an oxygen atom or occupies an oxygen vacancy site eliminating an electron trap while it may also attract hydrogen atoms thus favoring hydrogen doping. These multiple fluorine roles can reduce both the recombination losses and the electron extraction barrier at the ZnO/fullerene interface improving the selectivity of the cathode contact. Therefore, the fabricated devices using the fluorine plasma treated ZnO show high efficiency and stable characteristics, irrespective of the donor : acceptor combinations in the photoactive blend. Inverted polymer solar cells, consisting of the P3HT:PC71BM blend, exhibited increased lifetime and high power conversion efficiency (PCE) of 4.6%, while the ones with the PCDTBT:PC71BM blend exhibited a PCE of 6.9%. Our champion devices with the PTB7:PC71BM blends reached a high PCE of 8.0% and simultaneously showed exceptional environmental stability when using the fluorine passivated ZnO cathode interlayers

Avoiding ambient air and light induced degradation in high-efficiency polymer solar cells by the use of hydrogen-doped zinc oxide as electron extraction material

Polymer solar cells have undergone rapid development in recent years. Their limited stability to environmental influence and during illumination, however, still remains a major stumbling block to the commercial application of this technology. Several attempts have been made to address the instability issue, mostly concentrated on the insertion of charge transport interlayers in the device stack. Although zinc oxide (ZnO) is one of the most common electron transport materials in those cells, the presence of defects at the surface and grain boundaries significantly affects the efficiency and stability of the working devices. To address these issues, we herein employ hydrogen-doping of ZnO electron extraction material. It is found that devices based on photoactive layers composed of blends of poly(3-hexylthiophene) (P3HT) with electron acceptors possessing different energy levels, such as [6,6]-phenyl-C70butyric acid methyl ester (PC70BM) or indene-C60 bisadduct (IC60BA) essentially enhanced their photovoltaic performance when using the hydrogen-doped ZnO with maximum power conversion efficiency (PCE) reaching values of 4.62% and 6.65%, respectively, which are much higher than those of the cells with the pristine ZnO (3.08% and 4.51%). Most significantly, the degradation of non-encapsulated solar cells when exposed to ambient or under prolonged illumination is studied and it is found that devices based on un-doped ZnO showed poor environmental stability and significant photo-degradation while those using hydrogen-doped ZnO interlayers exhibited high long-term ambient stability and maintained nearly 80–90% of their initial PCE values after 40 h of 1.5 AM illumination. All mechanisms responsible for this enhanced stability are elucidated and corresponding models are proposed. This work successfully addresses and tackles the instability problem of polymer solar cells and the key findings pave the way for the upscaling of these and, perhaps, of related devices such as perovskite solar cells

Morphological changes in electrochemically deposited poly(3,4-ethylenedioxythiophene) films during overoxidation

Electrochemical and morphological properties of thin poly(3,4-ethylenedioxy-thiophene) (PEDOT) films deposited on gold were investigated in aqueous sulfuric acid solutions. X-ray diffraction and electron microscopy were used for monitoring the morphological changes and structure evolution caused by overoxidation. The diffraction peaks of PEDOT became sharper and more intensive during the subsequent oxidation cycles. This indicates that besides the degradation of the PEDOT film, its crystallinity was gradually improved with increasing the number of oxidation cycles. These changes may result in the appearance of novel properties that may be advantageous for specific applications