The operation of the GANIL control system

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aPKC regulates apical constriction to prevent tissue rupture in the Drosophila follicular epithelium

Funding: We thank Daniel St Johnston, Juergen Knoblich, Patrick Laprise, Stefano de Renzis, Xiaobo Wang, Yohanns Bellaiche, and the Bloomington and Kyoto Drosophila Stock Centers for reagents. We also thank Yohanns Bellaiche, Ivo Telley, and Romain Levayer for insightful comments on the manuscript. This work is funded by National Funds through FCT—Fundação para a Ciência e a Tecnologia, I.P., under the project PTDC/BIA-CEL/ 1511/2021. E.M.-d.-S.’s salary is funded by the ‘‘FCT Scientific Employment Stimulus’’ program. M.O.,A.B.-C., and A.M.C. were supported by PhD fellowships from FCT. M.O.’s salary was also supported by the Maria de Sousa Award Research in the J.J. lab was supported by Wellcome Trust, the Royal Society, and BBSRC (BB/V001353/1). The authors acknowledge the i3S Scientific Platform ALM, member of the national infrastructure Portuguese Platform of Bioimaging, and the Dundee Imaging Facility for excellent support.Apical-basal polarity is an essential epithelial trait controlled by the evolutionarily conserved PAR-aPKC polarity network. Dysregulation of polarity proteins disrupts tissue organization during development and in disease, but the underlying mechanisms are unclear due to the broad implications of polarity loss. Here, we uncover how Drosophila aPKC maintains epithelial architecture by directly observing tissue disorganization after fast optogenetic inactivation in living adult flies and ovaries cultured ex vivo. We show that fast aPKC perturbation in the proliferative follicular epithelium produces large epithelial gaps that result from increased apical constriction, rather than loss of apical-basal polarity. Accordingly, we can modulate the incidence of epithelial gaps by increasing and decreasing actomyosin-driven contractility. We traced the origin of these large epithelial gaps to tissue rupture next to dividing cells. Live imaging shows that aPKC perturbation induces apical constriction in non-mitotic cells within minutes, producing pulling forces that ultimately detach dividing and neighboring cells. We further demonstrate that epithelial rupture requires a global increase of apical constriction, as it is prevented by the presence of non-constricting cells. Conversely, a global induction of apical tension through light-induced recruitment of RhoGEF2 to the apical side is sufficient to produce tissue rupture. Hence, our work reveals that the roles of aPKC in polarity and actomyosin regulation are separable and provides the first in vivo evidence that excessive tissue stress can break the epithelial barrier during proliferation.proofepub_ahead_of_prin

Query Answering in Normal Logic Programs under Uncertainty

We present a simple, yet general top-down query answering procedure for normal logic programs over lattices and bilattices, where functions may appear in the rule bodies. Its interest relies on the fact that many approaches to paraconsistency and uncertainty in logic programs with or without non-monotonic negation are based on bilattices or lattices, respectively

Gravitational stability and dynamical overheating of stellar disks of galaxies

We use the marginal stability condition for galactic disks and the stellar velocity dispersion data published by different authors to place upper limits on the disk local surface density at two radial scalelengths $R=2h$. Extrapolating these estimates, we constrain the total mass of the disks and compare these estimates to those based on the photometry and color of stellar populations. The comparison reveals that the stellar disks of most of spiral galaxies in our sample cannot be substantially overheated and are therefore unlikely to have experienced a significant merging event in their history. The same conclusion applies to some, but not all of the S0 galaxies we consider. However, a substantial part of the early type galaxies do show the stellar velocity dispersion well in excess of the gravitational stability threshold suggesting a major merger event in the past. We find dynamically overheated disks among both seemingly isolated galaxies and those forming pairs. The ratio of the marginal stability disk mass estimate to the total galaxy mass within four radial scalelengths remains within a range of 0.4---0.8. We see no evidence for a noticeable running of this ratio with either the morphological type or color index.Comment: 25 pages, 5 figures, accepted to Astronomy Letter

The GANIL control system as seen from the control room

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Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases

The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy

Genome wide in silico SNP-tumor association analysis

BACKGROUND: Carcinogenesis occurs, at least in part, due to the accumulation of mutations in critical genes that control the mechanisms of cell proliferation, differentiation and death. Publicly accessible databases contain millions of expressed sequence tag (EST) and single nucleotide polymorphism (SNP) records, which have the potential to assist in the identification of SNPs overrepresented in tumor tissue. METHODS: An in silico SNP-tumor association study was performed utilizing tissue library and SNP information available in NCBI's dbEST (release 092002) and dbSNP (build 106). RESULTS: A total of 4865 SNPs were identified which were present at higher allele frequencies in tumor compared to normal tissues. A subset of 327 (6.7%) SNPs induce amino acid changes to the protein coding sequences. This approach identified several SNPs which have been previously associated with carcinogenesis, as well as a number of SNPs that now warrant further investigation CONCLUSIONS: This novel in silico approach can assist in prioritization of genes and SNPs in the effort to elucidate the genetic mechanisms underlying the development of cancer