Cancer cell lines show high heritability for motility but not generation time

Tumour evolution depends on heritable differences between cells in traits affecting cell survival or replication. It is well established that cancer cells are genetically and phenotypically heterogeneous; however, the extent to which this phenotypic variation is heritable is far less well explored. Here, we estimate the broad-sense heritability (H2) of two cell traits related to cancer hallmarks––cell motility and generation time––within populations of four cancer cell lines in vitro and find that motility is strongly heritable. This heritability is stable across multiple cell generations, with heritability values at the high end of those measured for a range of traits in natural populations of animals or plants. These findings confirm a central assumption of cancer evolution, provide a first quantification of the evolvability of key traits in cancer cells and indicate that there is ample raw material for experimental evolution in cancer cell lines. Generation time, a trait directly affecting cell fitness, shows substantially lower values of heritability than cell speed, consistent with its having been under directional selection removing heritable variation

New Associations of Gamma-Ray Sources from the Fermi Second Source Catalog

We present the results of an all-sky radio survey between 5 and 9 GHz of the fields surrounding all unassociated gamma-ray objects listed in the Fermi Large Area Telescope Second Source Catalog (2FGL). The goal of these observations is to find all new gamma-ray AGN associations with radio sources >10 mJy at 8 GHz. We observed with the Very Large Array and the Australia Telescope Compact Array the areas around unassociated sources, providing localizations of weak radio point sources found in 2FGL fields at arcmin scales. Then we followed-up a subset of those with the Very Long Baseline and the Long Baseline Arrays to confirm detections of radio emission on parsec-scales. We quantified association probabilities based on known statistics of source counts and assuming a uniform distribution of background sources. In total we found 865 radio sources at arcsec scales as candidates for association and detected 95 of 170 selected for follow-up observations at milliarcsecond resolution. Based on this we obtained firm associations for 76 previously unknown gamma-ray AGN. Comparison of these new AGN associations with the predictions from using the WISE color-color diagram shows that half of the associations are missed. We found that 129 out of 588 observed gamma-ray sources at arcmin scales not a single radio continuum source was detected above our sensitivity limit within the 3-sigma gamma-ray localization. These "empty" fields were found to be particularly concentrated at low Galactic latitudes. The nature of these Galactic gamma-ray emitters is not yet determined.Comment: accepted for publication by ApJS, 18 pages, 10 figures, 12 tables; full electronic versions of tables 2-8 are available as ancillary file

Resource competition promotes tumour expansion in experimentally evolved cancer

Tumour progression involves a series of phenotypic changes to cancer cells, each of which presents therapeutic targets. Here, using techniques adapted from microbial experimental evolution, we investigate the evolution of tumour spreading - a precursor for metastasis and tissue invasion - in environments with varied resource supply. Evolutionary theory predicts that competition for resources within a population will select for individuals to move away from a natal site (i.e. disperse), facilitating the colonisation of unexploited resources and decreasing competition between kin. After approximately 100 generations in environments with low resource supply, we find that MCF7 breast cancer spheroids (small in vitro tumours) show increased spreading. Conversely, spreading slows compared to the ancestor where resource supply is high. Common garden experiments confirm that the evolutionary responses differ between selection lines; with lines evolved under low resource supply showing phenotypic plasticity in spheroid spreading rate. These differences in spreading behaviour between selection lines are heritable (stable across multiple generations), and show that the divergently evolved lines differ in their response to resource supply. We observe dispersal-like behaviour and an increased sensitivity to resource availability in our selection lines, which may be a response to selection, or alternatively may be due to epigenetic changes, provoked by prolonged resource limitation, that have persisted across many cell generations. Different clinical strategies may be needed depending on whether or not tumour progression is due to natural selection. This study highlights the effectiveness of experimental evolution approaches in cancer cell populations and demonstrates how simple model systems might enable us to observe and measure key selective drivers of clinically important traits

Exact Numerical Solution of the BCS Pairing Problem

We propose a new simulation computational method to solve the reduced BCS Hamiltonian based on spin analogy and submatrix diagonalization. Then we further apply this method to solve superconducting energy gap and the results are well consistent with those obtained by Bogoliubov transformation method. The exponential problem of 2^{N}-dimension matrix is reduced to the polynomial problem of N-dimension matrix. It is essential to validate this method on a real quantumComment: 7 pages, 3 figure

Treatment recommendations for psoriatic arthritis

Objective: To develop comprehensive recommendations for the treatment of the various clinical manifestations of psoriatic arthritis (PsA) based on evidence obtained from a systematic review of the literature and from consensus opinion. Methods: Formal literature reviews of treatment for the most significant discrete clinical manifestations of PsA (skin and nails, peripheral arthritis, axial disease, dactylitis and enthesitis) were performed and published by members of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA). Treatment recommendations were drafted for each of the clinical manifestations by rheumatologists, dermatologists and PsA patients based on the literature reviews and consensus opinion. The level of agreement for the individual treatment recommendations among GRAPPA members was assessed with an online questionnaire. Results: Treatment recommendations were developed for peripheral arthritis, axial disease, psoriasis, nail disease, dactylitis and enthesitis in the setting of PsA. In rotal, 19 recommendations were drafted, and over 80% agreement was obtained on 16 of them. In addition, a grid that factors disease severity into each of the different disease manifestations was developed to help the clinician with treatment decisions for the individual patient from an evidenced-based perspective. Conclusions: Treatment recommendations for the cardinal physical manifestations of PsA were developed based on a literature review and consensus between rheumatologists and dermatologists. In addition, a grid was established to assist in therapeutic reasoning and decision making for individual patients. It is anticipated that periodic updates will take place using this framework as new data become available

The Low Quiescent X-Ray Luminosity of the Transient X-Ray Burster EXO 1747-214

We report on X-ray and optical observations of the X-ray burster EXO 1747-214. This source is an X-ray transient, and its only known outburst was observed in 1984-1985 by the EXOSAT satellite. We re-analyzed the EXOSAT data to derive the source position, column density, and a distance upper limit using its peak X-ray burst flux. We observed the EXO 1747-214 field in 2003 July with the Chandra X-ray Observatory to search for the quiescent counterpart. We found one possible candidate just outside the EXOSAT error circle, but we cannot rule out the possibility that the source is unrelated to EXO 1747-214. Our conclusion is that the upper limit on the unabsorbed 0.3-8 keV luminosity is L < 7E31 erg/s, making EXO 1747-214 one of the faintest neutron star transients in quiescence. We compare this luminosity upper limit to the quiescent luminosities of 19 neutron star and 14 black hole systems and discuss the results in the context of the differences between neutron stars and black holes. Based on the theory of deep crustal heating by Brown and coworkers, the luminosity implies an outburst recurrence time of >1300 yr unless some form of enhanced cooling occurs within the neutron star. The position of the possible X-ray counterpart is consistent with three blended optical/IR sources with R-magnitudes between 19.4 and 19.8 and J-magnitudes between 17.2 and 17.6. One of these sources could be the quiescent optical/IR counterpart of EXO 1747-214.Comment: 7 pages, accepted by the Astrophysical Journa

Peritoneal tissue-resident macrophages are metabolically poised to engage microbes using tissue-niche fuels

The importance of metabolism in macrophage function has been reported, but the in vivo relevance of the in vitro observations is still unclear. Here we show that macrophage metabolites are defined in a specific tissue context, and these metabolites are crucially linked to tissue-resident macrophage functions. We find the peritoneum to be rich in glutamate, a glutaminolysis-fuel that is exploited by peritoneal-resident macrophages to maintain respiratory burst during phagocytosis via enhancing mitochondrial complex-II metabolism. This niche-supported, inducible mitochondrial function is dependent on protein kinase C activity, and is required to fine-tune the cytokine responses that control inflammation. In addition, we find that peritoneal-resident macrophage mitochondria are recruited to phagosomes and produce mitochondrially derived reactive oxygen species, which are necessary for microbial killing. We propose that tissue-resident macrophages are metabolically poised in situ to protect and exploit their tissue-niche by utilising locally available fuels to implement specific metabolic programmes upon microbial sensing

Screening, intervention and outcome in autism and other developmental disorders: the role of randomized controlled trials

We draw attention to a number of important considerations in the arguments about screening and outcome of intervention in children with autism and other developmental disorders. Autism screening in itself never provides a final clinical diagnosis, but may well identify developmental deviations indicative of autism—or of other developmental disorders—that should lead to referral for further clinical assessment. Decisions regarding population or clinic screening cannot be allowed to be based on the fact that prospective longitudinal RCT designs over decades could never be performed in complex developmental disorders. We propose an alternative approach. Early screening for autism and other developmental disorders is likely to be of high societal importance and should be promoted and rigorously evaluated