A π-Extended Donor-Acceptor-Donor Triphenylene Twin linked via a Pyrazine-bridge

Beta-amino triphenylenes can be accessed via palladium catalyzed amination of the corresponding triflate using benzophe-none imine. Transformation of amine 6 to benzoyl amide 18 is also straightforward and its wide mesophase range demon-strates that the new linkage supports columnar liquid crystal formation. Amine 6 also undergoes clean aerobic oxidation to give a new twinned structure linked through an electron-poor pyrazine ring. The new discotic liquid crystal motif contains donor and acceptor fragments, and is more oval in shape rather than disk-like. It forms a wide range columnar mesophase. Absorption spectra are strong and broad; emission is also broad and occurs with a Stokes shift of ca. 0.7 eV, indicative of charge-transfer characte

Acquiring a pet dog significantly reduces stress of primary carers for children with autism spectrum disorder: a prospective case control study

This study describes the impact of pet dogs on stress of primary carers of children with Autism Spectrum Disorder (ASD). Stress levels of 38 primary carers acquiring a dog and 24 controls not acquiring a dog were sampled at: Pre-intervention (17 weeks before acquiring a dog), post-intervention (3–10 weeks after acquisition) and follow-up (25–40 weeks after acquisition), using the Parenting Stress Index. Analysis revealed significant improvements in the intervention compared to the control group for Total Stress, Parental Distress and Difficult Child. A significant number of parents in the intervention group moved from clinically high to normal levels of Parental Distress. The results highlight the potential of pet dogs to reduce stress in primary carers of children with an ASD

Stress in parents of children born very preterm is predicted by child externalising behaviour and parent coping at age 7 years

Objective: To examine factors which predict parenting stress in a longitudinal cohort of children born very preterm seen at age seven years.Methods: We recruited 100 very preterm (< 32 weeks GA) child-parent dyads and a control group of 50 term-born dyads born between 2001 and 2004 with follow-up at seven years. Parents completed the Parenting Stress Index, Ways of Coping Questionnaire, Child Behavior Check List, Beck Depression Inventory and the State Trait Anxiety Inventory questionnaires. Child IQ was assessed using the Wechsler Intelligence Scale-IV.Results: After controlling for maternal education, parents of preterm children (95% CI, 111.1 to 121.4) scored higher (p = .027) on the Parenting Stress Index than term born controls (95% CI, 97.8 to 113.2). Regression analyses showed that child externalising behaviour, sex and parent escape/avoidance coping style, predicted higher parenting stress in the preterm group. Parents of preterm girls expressed higher levels of stress than those of boys. Conclusions: Maladaptive coping strategies contribute to greater stress in parents of very preterm children. Our findings suggest that these parents need support for many years after birth of a very preterm infant

Radiosensitization of HNSCC cells by EGFR inhibition depends on the induction of cell cycle arrests

The increase in cellular radiosensitivity by EGF receptor (EGFR) inhibition has been shown to be attributable to the induction of a G1-arrest in p53-proficient cells. Because EGFR targeting in combination with radiotherapy is used to treat head and neck squamous cell carcinomas (HNSCC) which are predominantly p53 mutated, we tested the effects of EGFR targeting on cellular radiosensitivity, proliferation, apoptosis, DNA repair and cell cycle control using a large panel of HNSCC cell lines. In these experiments EGFR targeting inhibited signal transduction, blocked proliferation and induced radiosensitization but only in some cell lines and only under normal (pre-plating) conditions. This sensitization was not associated with impaired DNA repair (53BP1 foci) or induction of apoptosis. However, it was associated with the induction of a lasting G2-arrest. Both, the radiosensitization and the G2-arrest were abrogated if the cells were re-stimulated (delayed plating) with actually no radiosensitization being detectable in any of the 14 tested cell lines. Therefore we conclude that EGFR targeting can induce a reversible G2 arrest in p53 deficient HNSCC cells, which does not consequently result in a robust cellular radiosensitization. Together with recent animal and clinical studies our data indicate that EGFR inhibition is no effective strategy to increase the radiosensitivity of HNSCC cells.</p

Non-homologous DNA end joining in normal and cancer cells and its dependence on break structures

DNA double-strand breaks (DSBs) are a serious threat to the cell, for if not or miss-repaired, they can lead to chromosomal aberration, mutation and cancer. DSBs in human cells are repaired via non-homologous DNA end joining (NHEJ) and homologous recombination repair pathways. In the former process, the structure of DNA termini plays an important role, as does the genetic constitution of the cells, through being different in normal and pathological cells. In order to investigate the dependence of NHEJ on DSB structure in normal and cancer cells, we used linearized plasmids with various, complementary or non-complementary, single-stranded or blunt DNA termini, as well as whole-cell extract isolated from normal human lymphocytes, chronic myeloid leukemia K562 cells and lung cancer A549 cells. We observed a pronounced variability in the efficacy of NHEJ reaction depending on the type of ends. Plasmids with complementary and blunt termini were more efficiently repaired than the substrate with 3' protruding single-strand ends. The hierarchy of the effectiveness of NHEJ was on average, from the most effective to the least, A549/ normal lymphocytes/ K562. Our results suggest that the genetic constitution of the cells together with the substrate terminal structure may contribute to the efficacy of the NHEJ reaction. This should be taken into account on considering its applicability in cancer chemo- or radiotherapy by pharmacologically modulating NHEJ cellular responses

Consequences of conformational flexibility in hydrogen-bond-driven self-assembly processes

We report the synthesis and self-assembly of chiral, conformationally flexible C3-symmetrical trisamides. A strong Cotton effect is observed for the supramolecular polymers in linear alkanes but not in cyclic alkanes. MD simulations suggest 2:1 conformations of the amides within the aggregates in both types of solvents, but a chiral bias in only linear alkanes.JAB, MGI, RPAG, EWM and ARAP would like to thank the Gravity program 024.001.035, NWO TOP-PUNT 718.014.003 for financial support and Anneloes Oude Vrielink for TEM imaging. FDM and ML acknowledge the Swedish e-Research Center (SeRC) for financial support, the Swedish Research Council (Grant No. 621-2014-4646), SNIC (Swedish National Infrastructure for Computing) and Dr Julien Idé for providing the code for exciton coupling calculations

Early Detection, Diagnosis and Intervention Services for Young Children with Autism Spectrum Disorder in the European Union (ASDEU): Family and Professional Perspectives

Early services for ASD need to canvas the opinions of both parents and professionals. These opinions are seldom compared in the same research study. This study aims to ascertain the views of families and professionals on early detection, diagnosis and intervention services for young children with ASD. An online survey compiled and analysed data from 2032 respondents across 14 European countries (60.9% were parents; 39.1% professionals). Using an ordinal scale from 1 to 7, parents’ opinions were more negative (mean = 4.6; SD 2.2) compared to those of professionals (mean = 4.9; SD 1.5) when reporting satisfaction with services. The results suggest services should take into account child’s age, delays in accessing services, and active stakeholders’ participation when looking to improve services

A Systematic Proteomic Study of Irradiated DNA Repair Deficient Nbn-Mice

BACKGROUND: The NBN gene codes for the protein nibrin, which is involved in the detection and repair of DNA double strand breaks (DSBs). The NBN gene is essential in mammals. METHODOLOGY/PRINCIPAL FINDINGS: We have used a conditional null mutant mouse model in a proteomics approach to identify proteins with modified expression levels after 4 Gy ionizing irradiation in the absence of nibrin in vivo. Altogether, amongst approximately 8,000 resolved proteins, 209 were differentially expressed in homozygous null mutant mice in comparison to control animals. One group of proteins significantly altered in null mutant mice were those involved in oxidative stress and cellular redox homeostasis (p<0.0001). In substantiation of this finding, analysis of Nbn null mutant fibroblasts indicated an increased production of reactive oxygen species following induction of DSBs. CONCLUSIONS/SIGNIFICANCE: In humans, biallelic hypomorphic mutations in NBN lead to Nijmegen breakage syndrome (NBS), an autosomal recessive genetic disease characterised by extreme radiosensitivity coupled with growth retardation, immunoinsufficiency and a very high risk of malignancy. This particularly high cancer risk in NBS may be attributable to the compound effect of a DSB repair defect and oxidative stress