High-dose chemotherapy and autologous stem cell rescue for atypical teratoid/rhabdoid tumor of the central nervous system

Atypical Teratoid/Rhabdoid tumors (AT/RT) of the central nervous system are rare but aggressive tumors of childhood. Median survival with surgery and standard chemotherapy is less than 12 months. In an attempt to improve outcome, patients were treated with aggressive surgical resection and multi-agent chemotherapy, followed by high dose chemotherapy with autologous stem cell rescue. Nine consecutive children (median age 21 months) were diagnosed with AT/RT at the University of California San Francisco Childrens Hospital from 1997 to 2007 and treated with this aggressive approach. Diagnosis was confirmed using molecular markers. There are two long-term survivors (78 and 98 months from diagnosis). One additional patient is alive with disease. Three patients died of disease during therapy. Three patients died of disease after therapy was complete. There were no toxic deaths. Two of nine patients treated for AT/RT at our institution with high dose chemotherapy and autologous bone marrow transplant are long-term survivors, suggesting that a subset of patients can be cured with this approach

Outcomes of Brood Parasite–Host Interactions Mediated by Egg Matching: Common Cuckoos Cuculus canorus versus Fringilla Finches

Antagonistic species often interact via matching of phenotypes, and interactions between brood parasitic common cuckoos (Cuculus canorus) and their hosts constitute classic examples. The outcome of a parasitic event is often determined by the match between host and cuckoo eggs, giving rise to potentially strong associations between fitness and egg phenotype. Yet, empirical efforts aiming to document and understand the resulting evolutionary outcomes are in short supply.We used avian color space models to analyze patterns of egg color variation within and between the cuckoo and two closely related hosts, the nomadic brambling (Fringilla montifringilla) and the site fidelic chaffinch (F. coelebs). We found that there is pronounced opportunity for disruptive selection on brambling egg coloration. The corresponding cuckoo host race has evolved egg colors that maximize fitness in both sympatric and allopatric brambling populations. By contrast, the chaffinch has a more bimodal egg color distribution consistent with the evolutionary direction predicted for the brambling. Whereas the brambling and its cuckoo host race show little geographical variation in their egg color distributions, the chaffinch's distribution becomes increasingly dissimilar to the brambling's distribution towards the core area of the brambling cuckoo host race.High rates of brambling gene flow is likely to cool down coevolutionary hot spots by cancelling out the selection imposed by a patchily distributed cuckoo host race, thereby promoting a matching equilibrium. By contrast, the site fidelic chaffinch is more likely to respond to selection from adapting cuckoos, resulting in a markedly more bimodal egg color distribution. The geographic variation in the chaffinch's egg color distribution could reflect a historical gradient in parasitism pressure. Finally, marked cuckoo egg polymorphisms are unlikely to evolve in these systems unless the hosts evolve even more exquisite egg recognition capabilities than currently possessed

Cancer Genomics Identifies Regulatory Gene Networks Associated with the Transition from Dysplasia to Advanced Lung Adenocarcinomas Induced by c-Raf-1

Background: Lung cancer is a leading cause of cancer morbidity. To improve an understanding of molecular causes of disease a transgenic mouse model was investigated where targeted expression of the serine threonine kinase c-Raf to respiratory epithelium induced initialy dysplasia and subsequently adenocarcinomas. This enables dissection of genetic events associated with precancerous and cancerous lesions. Methodology/Principal Findings: By laser microdissection cancer cell populations were harvested and subjected to whole genome expression analyses. Overall 473 and 541 genes were significantly regulated, when cancer versus transgenic and non-transgenic cells were compared, giving rise to three distinct and one common regulatory gene network. At advanced stages of tumor growth predominately repression of gene expression was observed, but genes previously shown to be upregulated in dysplasia were also up-regulated in solid tumors. Regulation of developmental programs as well as epithelial mesenchymal and mesenchymal endothelial transition was a hall mark of adenocarcinomas. Additionaly, genes coding for cell adhesion, i.e. the integrins and the tight and gap junction proteins were repressed, whereas ligands for receptor tyrosine kinase such as epi- and amphiregulin were up-regulated. Notably, Vegfr- 2 and its ligand Vegfd, as well as Notch and Wnt signalling cascades were regulated as were glycosylases that influence cellular recognition. Other regulated signalling molecules included guanine exchange factors that play a role in an activation of the MAP kinases while several tumor suppressors i.e. Mcc, Hey1, Fat3, Armcx1 and Reck were significantly repressed. Finally, probable molecular switches forcing dysplastic cells into malignantly transformed cells could be identified. Conclusions/Significance: This study provides insight into molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity

First measurement of the |t|-dependence of coherent J/ψ photonuclear production

The first measurement of the cross section for coherent J/ψ photoproduction as a function of |t|, the square of the momentum transferred between the incoming and outgoing target nucleus, is presented. The data were measured with the ALICE detector in ultra-peripheral Pb–Pb collisions at a centre-of-mass energy per nucleon pair sNN=5.02TeV with the J/ψ produced in the central rapidity region |y|<0.8, which corresponds to the small Bjorken-x range (0.3−1.4)×10−3. The measured |t|-dependence is not described by computations based only on the Pb nuclear form factor, while the photonuclear cross section is better reproduced by models including shadowing according to the leading-twist approximation, or gluon-saturation effects from the impact-parameter dependent Balitsky–Kovchegov equation. These new results are therefore a valid tool to constrain the relevant model parameters and to investigate the transverse gluonic structure at very low Bjorken-x.publishedVersio

Resolving the strange behavior of extraterrestrial potassium in the upper atmosphere

It has been known since the 1960s that the layers of Na and K atoms, which occur between 80 and 105 km in the Earth's atmosphere as a result of meteoric ablation, exhibit completely different seasonal behavior. In the extratropics Na varies annually, with a pronounced wintertime maximum and summertime minimum. However, K varies semiannually with a small summertime maximum and minima at the equinoxes. This contrasting behavior has never been satisfactorily explained. Here we use a combination of electronic structure and chemical kinetic rate theory to determine two key differences in the chemistries of K and Na. First, the neutralization of K+ ions is only favored at low temperatures during summer. Second, cycling between K and its major neutral reservoir KHCO3 is essentially temperature independent. A whole atmosphere model incorporating this new chemistry, together with a meteor input function, now correctly predicts the seasonal behavior of the K layer