Parental cancer diagnosis and child mortality : a population-based cohort study in Sweden

OBJECTIVE: Cancer diagnosis is known to induce severe psychological stress for the diagnosed patients; however, how it affects the next-of-kin is less well documented. This study aimed to assess the impact of parental cancer on the risk of childhood death. METHODS: A population-based cohort study was conducted using the Swedish national registries, including 2,871,242 children followed during the period of 1991-2009. Parental cancer diagnosis was defined as a time-varying exposure. We used Cox proportional hazards regression to calculate the hazard ratio (HR) and its corresponding 95% confidence interval (CI) as an estimate of the association between parental cancer and childhood mortality. We adjusted for attained age, sex, gestational age, mode of delivery and birth weight of the child, maternal age at child's birth, as well as educational level and socio-economic classification of the parents in the analyses. RESULTS: Among 113,555 children with parental cancer, 127 deaths occurred during 561,198 person-years of follow-up. A parental cancer diagnosis was associated with an increased rate of death among children at the age of 1-18 (HR for all-cause death: 1.39; 95% CI: 1.16-1.66). For young children (aged 1-12), an increased rate was only noted for death due to cancer (HR: 2.06; 95% CI: 1.13-3.75) after parental cancer diagnosis. Among adolescents (aged 13-18), an increased rate was noted for all-cause death (HR: 1.52; 95% CI: 1.25-1.86), and for both non-cancer-related (HR: 1.43; 95% CI: 1.14-1.79) and cancer-related (HR: 2.07; 95% CI: 1.33-3.24) death in the exposed children. CONCLUSION: Children have an increased rate of death if they have a parent diagnosed with cancer as compared to children without such experience; this association appears to be slightly stronger among adolescents.Swedish Research CouncilSwedish Research Council for Health Working Life & Welfare (Forte), 2012-0498Swedish Research Council SIMSAM, 80748301, 340-2013-5867China Scholarship Council, 201206100002Swedish Society for Medical Research (SSMF)Karolinska InstitutetPublishe

Hot dense capsule implosion cores produced by z-pinch dynamic hohlraum radiation

Hot dense capsule implosions driven by z-pinch x-rays have been measured for the first time. A ~220 eV dynamic hohlraum imploded 1.7-2.1 mm diameter gas-filled CH capsules which absorbed up to ~20 kJ of x-rays. Argon tracer atom spectra were used to measure the Te~ 1keV electron temperature and the ne ~ 1-4 x10^23 cm-3 electron density. Spectra from multiple directions provide core symmetry estimates. Computer simulations agree well with the peak compression values of Te, ne, and symmetry, indicating reasonable understanding of the hohlraum and implosion physics.Comment: submitted to Phys. Rev. Let

Parental bereavement and the loss of purpose in life as a function of interdependent self-construal

Citation: Parental bereavement and the loss of purpose in life as a function of interdependent self-construal. Front. Psychol. 6:1078. doi: 10.3389/fpsyg.2015 Parental bereavement and the loss of purpose in life as a function of interdependent self-construal Children are often inextricably linked to their parents' hopes and dreams. As such, the loss of a child often represents one of the most traumatic experiences possible. The current research explores how this specific loss relates to one's sense of purpose in life. We further explore whether the loss of a child is particularly detrimental to one's sense of purpose for highly interdependent parents. Analyses of parents from the Midlife in the United States data set revealed, as expected, that the loss of child negatively predicts one's sense of purpose in life, and that this effect is most pronounced for parents high in interdependent self-construal. Potential mechanisms and implications of the present findings are discussed

Growth arrest-specific gene 6 expression in human breast cancer

Growth arrest-specific gene 6 (Gas6), identified in 1995, acts as the ligand to the Axl/Tyro3 family of tyrosine kinase receptors and exerts mitogenic activity when bound to these receptors. Overexpression of the Axl/Tyro3 receptor family has been found in breast, ovarian and lung tumours. Gas6 is upregulated 23-fold by progesterone acting through the progesterone receptor B (PRB). Recently, Gas6 has been shown to be a target for overexpression and amplification in breast cancer. Quantitative real-time PCR analysis was used to determine the levels of Gas6 mRNA expression in 49 primary breast carcinomas. Expression of PRB protein was evaluated immunohistochemically with a commercially available PRB antibody. The results showed a positive association between PRB protein and Gas6 mRNA levels (P=0.04). Gas6 correlated positively with a number of favourable prognostic variables including lymph node negativity (P=0.0002), younger age at diagnosis (P=0.04), smaller size of tumours (P=0.02), low Nottingham prognostic index scores (P=0.03) and low nuclear morphology (P=0.03). This study verifies for the first time the association between PRB and Gas6 in breast cancer tissue

Capsule design for the National Ignition Facility

Several choices exist in the design and production of capsules intended to ignite and propagate fusion burn of the DT fuel when imploded by indirect drive at the National Ignition Facility. These choices include ablator material, ablator dopant concentration and distribution, capsule dimensions, and x-ray drive profile (shock timings and strengths). The choice of ablator material must also include fabrication and material characteristics, such as attainable surface finishes, permeability, strength, transparency to radio frequency and infrared radiation, thermal conductivity, and material homogeneity. Understanding the advantages and/or limitations of these choices is an ongoing effort for LLNL and LANL designers. At this time, simulations in one- two- and three- dimensions show that capsules with either a copper doped beryllium or a polyimide (C22H10N2O4) ablator material have both the least sensitivity to initial surface roughnesses and favorable fabrication qualities. Simulations also indicate the existence of capsule designs based on these ablator materials which ignite and burn when imploded by less than nominal laser performance (900 kJ energy, 250 TW power, producing 250 eV peak radiation temperature). We will describe and compare these reduced scale capsules, in addition to several designs which use the expected 300 eV peak x-ray drive obtained from the nominal NIF laser (1.3 MJ, 500 TW)

A “Coiled-Coil” Motif Is Important for Oligomerization and DNA Binding Properties of Human Cytomegalovirus Protein UL77

Human cytomegalovirus (HCMV) UL77 gene encodes the essential protein UL77, its function is characterized in the present study. Immunoprecipitation identified monomeric and oligomeric pUL77 in HCMV infected cells. Immunostaining of purified virions and subviral fractions showed that pUL77 is a structural protein associated with capsids. In silico analysis revealed the presence of a coiled-coil motif (CCM) at the N-terminus of pUL77. Chemical cross-linking of either wild-type pUL77 or CCM deletion mutant (pUL77ΔCCM) implicated that CCM is critical for oligomerization of pUL77. Furthermore, co-immunoprecipitations of infected and transfected cells demonstrated that pUL77 interacts with the capsid-associated DNA packaging motor components, pUL56 and pUL104, as well as the major capsid protein. The ability of pUL77 to bind dsDNA was shown by an in vitro assay. Binding to certain DNA was further confirmed by an assay using biotinylated 36-, 250-, 500-, 1000-meric dsDNA and 966-meric HCMV-specific dsDNA designed for this study. The binding efficiency (BE) was determined by image processing program defining values above 1.0 as positive. While the BE of the pUL56 binding to the 36-mer bio-pac1 containing a packaging signal was 10.0±0.63, the one for pUL77 was only 0.2±0.03. In contrast to this observation the BE of pUL77 binding to bio-500 bp or bio-1000 bp was 2.2±0.41 and 4.9±0.71, respectively. By using pUL77ΔCCM it was demonstrated that this protein could not bind to dsDNA. These data indicated that pUL77 (i) could form homodimers, (ii) CCM of pUL77 is crucial for oligomerization and (iii) could bind to dsDNA in a sequence independent manner

NOTCH1 Signaling Promotes Human T-Cell Acute Lymphoblastic Leukemia Initiating Cell Regeneration in Supportive Niches

Leukemia initiating cells (LIC) contribute to therapeutic resistance through acquisition of mutations in signaling pathways, such as NOTCH1, that promote self-renewal and survival within supportive niches. Activating mutations in NOTCH1 occur commonly in T cell acute lymphoblastic leukemia (T-ALL) and have been implicated in therapeutic resistance. However, the cell type and context specific consequences of NOTCH1 activation, its role in human LIC regeneration, and sensitivity to NOTCH1 inhibition in hematopoietic microenvironments had not been elucidated.We established humanized bioluminescent T-ALL LIC mouse models transplanted with pediatric T-ALL samples that were sequenced for NOTCH1 and other common T-ALL mutations. In this study, CD34(+) cells from NOTCH1(Mutated) T-ALL samples had higher leukemic engraftment and serial transplantation capacity than NOTCH1(Wild-type) CD34(+) cells in hematopoietic niches, suggesting that self-renewing LIC were enriched within the NOTCH1(Mutated) CD34(+) fraction. Humanized NOTCH1 monoclonal antibody treatment reduced LIC survival and self-renewal in NOTCH1(Mutated) T-ALL LIC-engrafted mice and resulted in depletion of CD34(+)CD2(+)CD7(+) cells that harbor serial transplantation capacity.These results reveal a functional hierarchy within the LIC population based on NOTCH1 activation, which renders LIC susceptible to targeted NOTCH1 inhibition and highlights the utility of NOTCH1 antibody targeting as a key component of malignant stem cell eradication strategies

BST2/Tetherin Enhances Entry of Human Cytomegalovirus

Interferon-induced BST2/Tetherin prevents budding of vpu-deficient HIV-1 by tethering mature viral particles to the plasma membrane. BST2 also inhibits release of other enveloped viruses including Ebola virus and Kaposi's sarcoma associated herpesvirus (KSHV), indicating that BST2 is a broadly acting antiviral host protein. Unexpectedly however, recovery of human cytomegalovirus (HCMV) from supernatants of BST2-expressing human fibroblasts was increased rather than decreased. Furthermore, BST2 seemed to enhance viral entry into cells since more virion proteins were released into BST2-expressing cells and subsequent viral gene expression was elevated. A significant increase in viral entry was also observed upon induction of endogenous BST2 during differentiation of the pro-monocytic cell line THP-1. Moreover, treatment of primary human monocytes with siRNA to BST2 reduced HCMV infection, suggesting that BST2 facilitates entry of HCMV into cells expressing high levels of BST2 either constitutively or in response to exogenous stimuli. Since BST2 is present in HCMV particles we propose that HCMV entry is enhanced via a reverse-tethering mechanism with BST2 in the viral envelope interacting with BST2 in the target cell membrane. Our data suggest that HCMV not only counteracts the well-established function of BST2 as inhibitor of viral egress but also employs this anti-viral protein to gain entry into BST2-expressing hematopoietic cells, a process that might play a role in hematogenous dissemination of HCMV

Family Matters:Rethinking the Psychology of Human Social Motivation

What motives do people prioritize in their social lives? Historically, social psychologists, especially those adopting an evolutionary perspective, have devoted a great deal of research attention to sexual attraction and romantic-partner choice (mate seeking). Research on long-term familial bonds (mate retention and kin care) has been less thoroughly connected to relevant comparative and evolutionary work on other species, and in the case of kin care, these bonds have been less well researched. Examining varied sources of data from 27 societies around the world, we found that people generally view familial motives as primary in importance and mate-seeking motives as relatively low in importance. Compared with other groups, college students, single people, and men place relatively higher emphasis on mate seeking, but even those samples rated kin-care motives as more important. Furthermore, motives linked to long-term familial bonds are positively associated with psychological well-being, but mate-seeking motives are associated with anxiety and depression. We address theoretical and empirical reasons why there has been extensive research on mate seeking and why people prioritize goals related to long-term familial bonds over mating goals. Reallocating relatively greater research effort toward long-term familial relationships would likely yield many interesting new findings relevant to everyday people’s highest social priorities

Evolutionarily Conserved Herpesviral Protein Interaction Networks

Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeast-two-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species