DICER1 tumor predisposition syndrome: An evolving story initiated with the pleuropulmonary blastoma

DICER1 syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous DICER1 germline mutation. The most common tumor seen clinically is the pleuropulmonary blastoma (PPB), a lung neoplasm of early childhood which is classified on its morphologic features into four types (IR, I, II and III) with tumor progression over time within the first 4-5 years of life from the prognostically favorable cystic type I to the unfavorable solid type III. Following the initial report of PPB, its association with other cystic neoplasms was demonstrated in family studies. The detection of the germline mutation in DICER1 provided the opportunity to identify and continue to recognize a number seemingly unrelated extrapulmonary neoplasms: Sertoli-Leydig cell tumor, gynandroblastoma, embryonal rhabdomyosarcomas of the cervix and other sites, multinodular goiter, differentiated and poorly differentiated thyroid carcinoma, cervical-thyroid teratoma, cystic nephroma-anaplastic sarcoma of kidney, nasal chondromesenchymal hamartoma, intestinal juvenile-like hamartomatous polyp, ciliary body medulloepithelioma, pituitary blastoma, pineoblastoma, primary central nervous system sarcoma, embryonal tumor with multilayered rosettes-like cerebellar tumor, PPB-like peritoneal sarcoma, DICER1-associated presacral malignant teratoid neoplasm and other non-neoplastic associations. Each of these neoplasms is characterized by a second somatic mutation in DICER1. In this review, we have summarized the salient clinicopathologic aspects of these tumors whose histopathologic features have several overlapping morphologic attributes particularly the primitive mesenchyme often with rhabdomyoblastic and chondroid differentiation and an uncommitted spindle cell pattern. Several of these tumors have an initial cystic stage from which there is progression to a high grade, complex patterned neoplasm. These pathologic findings in the appropriate clinical setting should serve to alert the pathologist to the possibility of a DICER1-associated neoplasm and initiate appropriate testing on the neoplasm and to alert the clinician about the concern for a DICER1 mutation

Relativistic and Binding Energy Corrections to Direct Photon Production In Upsilon Decay

A systematic gauge-invariant method is used to calculate the rate for an upsilon meson to decay inclusively into a prompt photon. An expansion is made in the quark relative velocity v, which is a small natural parameter for heavy quark systems. Inclusion of these O(v^2) corrections tends to increase the photon rate in the middle z range and to lower it for larger z, a feature supported by the data.Comment: 13 pages, LateX, One figure (to be published in Phys. Rev. D, Sept. 1, 1996

Interleukin-7 deficiency in rheumatoid arthritis: consequences for therapy-induced lymphopenia

We previously demonstrated prolonged, profound CD4+ T-lymphopenia in rheumatoid arthritis (RA) patients following lymphocyte-depleting therapy. Poor reconstitution could result either from reduced de novo T-cell production through the thymus or from poor peripheral expansion of residual T-cells. Interleukin-7 (IL-7) is known to stimulate the thymus to produce new T-cells and to allow circulating mature T-cells to expand, thereby playing a critical role in T-cell homeostasis. In the present study we demonstrated reduced levels of circulating IL-7 in a cross-section of RA patients. IL-7 production by bone marrow stromal cell cultures was also compromised in RA. To investigate whether such an IL-7 deficiency could account for the prolonged lymphopenia observed in RA following therapeutic lymphodepletion, we compared RA patients and patients with solid cancers treated with high-dose chemotherapy and autologous progenitor cell rescue. Chemotherapy rendered all patients similarly lymphopenic, but this was sustained in RA patients at 12 months, as compared with the reconstitution that occurred in cancer patients by 3–4 months. Both cohorts produced naïve T-cells containing T-cell receptor excision circles. The main distinguishing feature between the groups was a failure to expand peripheral T-cells in RA, particularly memory cells during the first 3 months after treatment. Most importantly, there was no increase in serum IL-7 levels in RA, as compared with a fourfold rise in non-RA control individuals at the time of lymphopenia. Our data therefore suggest that RA patients are relatively IL-7 deficient and that this deficiency is likely to be an important contributing factor to poor early T-cell reconstitution in RA following therapeutic lymphodepletion. Furthermore, in RA patients with stable, well controlled disease, IL-7 levels were positively correlated with the T-cell receptor excision circle content of CD4+ T-cells, demonstrating a direct effect of IL-7 on thymic activity in this cohort

Silicon Nanoparticles: Source of Extended Red Emission?

We have reviewed the characteristics of the extended red emission (ERE) as observed in many dusty astronomical environments, in particular, the diffuse interstellar medium of the Galaxy. The spectral nature and the photon conversion efficiency of the ERE identify the underlying process as highly efficient photoluminescence by an abundant component of interstellar dust. We have compared the photoluminescence properties of a variety of carbon- and silicon-based materials proposed as sources for the ERE with the observationally established constraints. We found that silicon nanoparticles provide the best match to the spectrum and the efficiency requirement of the ERE. If present in interstellar space with an abundance sufficient to explain the intensity of the ERE, silicon nanoparticles will also contribute to the interstellar 9.7 micron Si-O stretch feature in absorption, to the near- and mid-IR nonequilibrium thermal background radiation, and to the continuum extinction in the near- and far-UV. About 36% of the interstellar silicon depleted into the dust phase would be needed in the form of silicon nanoparticles, amounting to less than 5% of the interstellar dust mass. We propose that silicon nanoparticles form through the nucleation of SiO in oxygen-rich stellar mass outflows and that they represent an important small-grain component of the interstellar dust spectrum.Comment: 5 pages; 1 included figure; accepted 1998 May 1, ApJ

The endorsement of cognitive distortions: comparing child pornography offenders and contact sex offenders

This study examined the endorsement of cognitive distortions in child pornography offenders (CPOs), using an established assessment tool, the Abel and Becker Cognition Scale. The scale was expanded to include cognitions specific to child pornography offending, extracted from Howitt and Sheldon’s Children and Sexual Activities Inventory (C&SA). Three samples of CPOs, child sex offenders and offenders with both offence types responded to the cognition items. An exploratory Principal Component Analysis suggested six main components of the scale. CPOs were significantly less likely to endorse these statements in general, and this was more pronounced on items that project blame onto the child or other people, describe a need for power and consider children as sexually active. The statements extracted from C&SA did not differentiate between the groups. These findings are discussed under consideration of the relationship between cognitive distortions and contact sex offending, and in reference to the general criticism concerning the definition and appropriate measurement of cognitive distortion

Uncanny Objects and the Fear of the Familiar:Hiding from Akan Witches in New York City

This article examines the cosmology and secret practices of West African traditional priests in New York City in preventing the spread of witchcraft, an evil invisible spirit transmitted between female members of the Akan matrilineage. Explored is an uncanny dynamic as everyday habitus becomes increasingly strange in the world of a young Ghanaian woman in the Bronx, who has become petrified of insinuations of witchcraft from close family members. In trying to hide the young woman from infection by her fellow witches, Akan priests attempt to ‘capture’ her habits and everyday routines, calling upon the iconic magic of New York City in order to ‘misplace’ familiarity within the anonymity of Manhattan. In this process, the transmission of the witch’s spirit to the intended victim is disturbed as the victim’s life and things are moved. Nowhere to be found, the witch shifts her attention to other victims

Context Matters: The Illusive Simplicity of Macaque V1 Receptive Fields

Even in V1, where neurons have well characterized classical receptive fields (CRFs), it has been difficult to deduce which features of natural scenes stimuli they actually respond to. Forward models based upon CRF stimuli have had limited success in predicting the response of V1 neurons to natural scenes. As natural scenes exhibit complex spatial and temporal correlations, this could be due to surround effects that modulate the sensitivity of the CRF. Here, instead of attempting a forward model, we quantify the importance of the natural scenes surround for awake macaque monkeys by modeling it non-parametrically. We also quantify the influence of two forms of trial to trial variability. The first is related to the neuron’s own spike history. The second is related to ongoing mean field population activity reflected by the local field potential (LFP). We find that the surround produces strong temporal modulations in the firing rate that can be both suppressive and facilitative. Further, the LFP is found to induce a precise timing in spikes, which tend to be temporally localized on sharp LFP transients in the gamma frequency range. Using the pseudo R[superscript 2] as a measure of model fit, we find that during natural scene viewing the CRF dominates, accounting for 60% of the fit, but that taken collectively the surround, spike history and LFP are almost as important, accounting for 40%. However, overall only a small proportion of V1 spiking statistics could be explained (R[superscript 2]~5%), even when the full stimulus, spike history and LFP were taken into account. This suggests that under natural scene conditions, the dominant influence on V1 neurons is not the stimulus, nor the mean field dynamics of the LFP, but the complex, incoherent dynamics of the network in which neurons are embedded.National Institutes of Health (U.S.) (K25 NS052422-02)National Institutes of Health (U.S.) (DP1 ODOO3646

Grain Surface Models and Data for Astrochemistry

AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions

Microorganisms from aphid honeydew attract and enhance the efficacy of natural enemies

Aphids are one of the most serious pests of crops worldwide, causing major yield and economic losses. To control aphids, natural enemies could be an option but their efficacy is sometimes limited by their dispersal in natural environment. Here we report the first isolation of a bacterium from the pea aphid Acyrthosiphon pisum honeydew, Staphylococcus sciuri, which acts as a kairomone enhancing the efficiency of aphid natural enemies. Our findings represent the first case of a host-associated bacterium driving prey location and ovipositional preference for the natural enemy. We show that this bacterium has a key role in tritrophic interactions because it is the direct source of volatiles used to locate prey. Some specific semiochemicals produced by S. sciuri were also identified as significant attractants and ovipositional stimulants. The use of this host-associated bacterium could certainly provide a novel approach to control aphids in field and greenhouse systems