Site-dependent charge transfer at the Pt(111)-ZnPc interface and the effect of iodine

The electronic structure of ZnPc, from sub-monolayers to thick films, on bare and iodated Pt(111) is studied by means of X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS) and scanning tunneling microscopy (STM). Our results suggest that at low coverage ZnPc lies almost parallel to the Pt(111) substrate, in a non-planar configuration induced by Zn-Pt attraction, leading to an inhomogeneous charge distribution within the molecule and charge transfer to the molecule. ZnPc does not form a complete monolayer on the Pt surface, due to a surface-mediated intermolecular repulsion. At higher coverage ZnPc adopts a tilted geometry, due to a reduced molecule-substrate interaction. Our photoemission results illustrate that ZnPc is practically decoupled from Pt, already from the second layer. Pre-deposition of iodine on Pt hinders the Zn-Pt attraction, leading to a non-distorted first layer ZnPc in contact with Pt(111)-I $\left(\sqrt{3}\times\sqrt{3}\right)$ or Pt(111)-I $\left(\sqrt{7}\times\sqrt{7}\right)$, and a more homogeneous charge distribution and charge transfer at the interface. On increased ZnPc thickness iodine is dissolved in the organic film where it acts as an electron acceptor dopant.Comment: 12 pages, 9 figure

Effect of Pentavac and measles-mumps-rubella (MMR) vaccination on the intestine

To access full text version of this article. Please click on the hyperlink "Full Text" at the bottom of this pageBACKGROUND: The safety of infant vaccination has been questioned in recent years. In particular it has been suggested that the measles, mumps, and rubella (MMR) vaccination leads to brain damage manifesting as autism consequent to the development of an "enterocolitis" in the immediate post-vaccination period. AIM: To assess if MMR vaccination is associated with subclinical intestinal inflammation, which is central to the autistic "enterocolitis" theory. METHODS: We studied 109/58 infants, before and two and four weeks after immunisation with Pentavac and MMR vaccines, for the presence of intestinal inflammation (faecal calprotectin). RESULTS: Neither vaccination was associated with any significant increase in faecal calprotectin concentrations. CONCLUSIONS: The failure of the MMR vaccination to cause an intestinal inflammatory response provides evidence against the proposed gut-brain interaction that is central to the autistic "enterocolitis" hypothesis

Comparing resonant photon tunneling via cavity modes and Tamm plasmon polariton modes in metal-coated Bragg mirrors

Resonant photon tunneling was investigated experimentally in multilayer structures containing a high-contrast (TiO2/SiO2) Bragg mirror capped with a semitransparent gold film. Transmission via a fundamental cavity resonance was compared with transmission via the Tamm plasmon polariton resonance that appears at the interface between a metal film and a one-dimensional photonic bandgap structure. The Tamm-plasmon-mediated transmission exhibits a smaller dependence on the angle and polarization of the incident light for similar values of peak transmission, resonance wavelength, and finesse. Implications for transparent electrical contacts based on resonant tunneling structures are discussed

High expression of ZNF703 independent of amplification indicates worse prognosis in patients with luminal B breast cancer

Peer reviewe

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM -/- patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

Kretzoiarctos gen. nov., the Oldest Member of the Giant Panda Clade

The phylogenetic position of the giant panda, Ailuropoda melanoleuca (Carnivora: Ursidae: Ailuropodinae), has been one of the most hotly debated topics by mammalian biologists and paleontologists during the last century. Based on molecular data, it is currently recognized as a true ursid, sister-taxon of the remaining extant bears, from which it would have diverged by the Early Miocene. However, from a paleobiogeographic and chronological perspective, the origin of the giant panda lineage has remained elusive due to the scarcity of the available Miocene fossil record. Until recently, the genus Ailurarctos from the Late Miocene of China (ca. 8–7 mya) was recognized as the oldest undoubted member of the Ailuropodinae, suggesting that the panda lineage might have originated from an Ursavus ancestor. The role of the purported ailuropodine Agriarctos, from the Miocene of Europe, in the origins of this clade has been generally dismissed due to the paucity of the available material. Here, we describe a new ailuropodine genus, Kretzoiarctos gen. nov., based on remains from two Middle Miocene (ca. 12–11 Ma) Spanish localities. A cladistic analysis of fossil and extant members of the Ursoidea confirms the inclusion of the new genus into the Ailuropodinae. Moreover, Kretzoiarctos precedes in time the previously-known, Late Miocene members of the giant panda clade from Eurasia (Agriarctos and Ailurarctos). The former can be therefore considered the oldest recorded member of the giant panda lineage, which has significant implications for understanding the origins of this clade from a paleobiogeographic viewpoint

Insertion of an SVA-E retrotransposon into the CASP8 gene is associated with protection against prostate cancer

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Transcriptional and splicing anomalies have been observed in intron 8 of the CASP8 gene (encoding procaspase-8) in association with cutaneous basal-cell carcinoma (BCC) and linked to a germline SNP rs700635. Here, we show that the rs700635[C] allele, which is associated with increased risk of BCC and breast cancer, is protective against prostate cancer [odds ratio (OR) = 0.91, P = 1.0 × 10(-6)]. rs700635[C] is also associated with failures to correctly splice out CASP8 intron 8 in breast and prostate tumours and in corresponding normal tissues. Investigation of rs700635[C] carriers revealed that they have a human-specific short interspersed element-variable number of tandem repeat-Alu (SINE-VNTR-Alu), subfamily-E retrotransposon (SVA-E) inserted into CASP8 intron 8. The SVA-E shows evidence of prior activity, because it has transduced some CASP8 sequences during subsequent retrotransposition events. Whole-genome sequence (WGS) data were used to tag the SVA-E with a surrogate SNP rs1035142[T] (r(2) = 0.999), which showed associations with both the splicing anomalies (P = 6.5 × 10(-32)) and with protection against prostate cancer (OR = 0.91, P = 3.8 × 10(-7)).National Cancer Research Institute (NCRI) G0500966/75466 Department of Health, Medical Research Council Cancer Research UK University of Cambridge NIHR Department of Health Anniversary Fund of the Austrian National Bank 15079 Medical and Scientific Fund of the Mayor of the City of Vienna 10077 Common Fund of the Office of the Director of the National Institutes of Health NCI NHGRI NHLBI NIDA NIMH NINDS NCI\SAIC-Frederick, Inc. (SAIC-F) 10XS170 Roswell Park Cancer Institute 10XS171 Science Care, Inc. X10S172 SAIC-F 10ST1035 HHSN261200800001E deCODE genetics/AMGEN HHSN268201000029C DA006227 DA033684 N01MH000028 MH090941 MH101814 MH090951 MH090937 MH101820 MH101825 MH090936 MH101819 MH090948 MH101782 MH101810 MH10182

Genetic correction of PSA values using sequence variants associated with PSA levels

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldMeasuring serum levels of the prostate-specific antigen (PSA) is the most common screening method for prostate cancer. However, PSA levels are affected by a number of factors apart from neoplasia. Notably, around 40% of the variability of PSA levels in the general population is accounted for by inherited factors, suggesting that it may be possible to improve both sensitivity and specificity by adjusting test results for genetic effects. To search for sequence variants that associate with PSA levels, we performed a genome-wide association study and follow-up analysis using PSA information from 15,757 Icelandic and 454 British men not diagnosed with prostate cancer. Overall, we detected a genome-wide significant association between PSA levels and single-nucleotide polymorphisms (SNPs) at six loci: 5p15.33 (rs2736098), 10q11 (rs10993994), 10q26 (rs10788160), 12q24 (rs11067228), 17q12 (rs4430796), and 19q13.33 [rs17632542 (KLK3: I179T)], each with P(combined) <3 × 10(-10). Among 3834 men who underwent a biopsy of the prostate, the 10q26, 12q24, and 19q13.33 alleles that associate with high PSA levels are associated with higher probability of a negative biopsy (odds ratio between 1.15 and 1.27). Assessment of association between the six loci and prostate cancer risk in 5325 cases and 41,417 controls from Iceland, the Netherlands, Spain, Romania, and the United States showed that the SNPs at 10q26 and 12q24 were exclusively associated with PSA levels, whereas the other four loci also were associated with prostate cancer risk. We propose that a personalized PSA cutoff value, based on genotype, should be used when deciding to perform a prostate biopsy.info:eu-repo/grantAgreement/EC/FP7/202059/ 218071 Urological Research Foundation P50 CA90386-05S2 Robert H. Lurie Comprehensive Cancer Center p30 CA60553 Health Technology Assessment Programme 96/20/06 96/20/99 Department of Health, England Cancer Research UK C522/A8649 Medical Research Council of England G0500966 ID 75466 National Cancer Research Institute (NCRI), UK Southwest National Health Service Research and Development NCRI National Institute for Health Resear