| 1. |
- Martrat, Griselda, et al.
(författare)
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Exploring the link between MORF4L1 and risk of breast cancer
- 2011
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Ingår i: Breast Cancer Research. - : Springer Science and Business Media LLC. - 1465-5411 .- 1465-542X. ; 13:2
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Proteins encoded by Fanconi anemia (FA) and/or breast cancer (BrCa) susceptibility genes cooperate in a common DNA damage repair signaling pathway. To gain deeper insight into this pathway and its influence on cancer risk, we searched for novel components through protein physical interaction screens. Methods: Protein physical interactions were screened using the yeast two-hybrid system. Co-affinity purifications and endogenous co-immunoprecipitation assays were performed to corroborate interactions. Biochemical and functional assays in human, mouse and Caenorhabditis elegans models were carried out to characterize pathway components. Thirteen FANCD2-monoubiquitinylation-positive FA cell lines excluded for genetic defects in the downstream pathway components and 300 familial BrCa patients negative for BRCA1/2 mutations were analyzed for genetic mutations. Common genetic variants were genotyped in 9,573 BRCA1/2 mutation carriers for associations with BrCa risk. Results: A previously identified co-purifying protein with PALB2 was identified, MRG15 (MORF4L1 gene). Results in human, mouse and C. elegans models delineate molecular and functional relationships with BRCA2, PALB2, RAD51 and RPA1 that suggest a role for MRG15 in the repair of DNA double-strand breaks. Mrg15-deficient murine embryonic fibroblasts showed moderate sensitivity to g-irradiation relative to controls and reduced formation of Rad51 nuclear foci. Examination of mutants of MRG15 and BRCA2 C. elegans orthologs revealed phenocopy by accumulation of RPA-1 (human RPA1) nuclear foci and aberrant chromosomal compactions in meiotic cells. However, no alterations or mutations were identified for MRG15/MORF4L1 in unclassified FA patients and BrCa familial cases. Finally, no significant associations between common MORF4L1 variants and BrCa risk for BRCA1 or BRCA2 mutation carriers were identified: rs7164529, P-trend = 0.45 and 0.05, P-2df = 0.51 and 0.14, respectively; and rs10519219, P-trend = 0.92 and 0.72, P-2df = 0.76 and 0.07, respectively. Conclusions: While the present study expands on the role of MRG15 in the control of genomic stability, weak associations cannot be ruled out for potential low-penetrance variants at MORF4L1 and BrCa risk among BRCA2 mutation carriers.
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| 2. |
- Maxwell, Christopher A., et al.
(författare)
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Interplay between BRCA1 and RHAMM Regulates Epithelial Apicobasal Polarization and May Influence Risk of Breast Cancer
- 2011
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Ingår i: PLoS Biology. - : Public Library of Science (PLoS). - 1545-7885 .- 1544-9173. ; 9:11
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Tidskriftsartikel (refereegranskat)abstract
- Differentiated mammary epithelium shows apicobasal polarity, and loss of tissue organization is an early hallmark of breast carcinogenesis. In BRCA1 mutation carriers, accumulation of stem and progenitor cells in normal breast tissue and increased risk of developing tumors of basal-like type suggest that BRCA1 regulates stem/progenitor cell proliferation and differentiation. However, the function of BRCA1 in this process and its link to carcinogenesis remain unknown. Here we depict a molecular mechanism involving BRCA1 and RHAMM that regulates apicobasal polarity and, when perturbed, may increase risk of breast cancer. Starting from complementary genetic analyses across families and populations, we identified common genetic variation at the low-penetrance susceptibility HMMR locus (encoding for RHAMM) that modifies breast cancer risk among BRCA1, but probably not BRCA2, mutation carriers: n = 7,584, weighted hazard ratio ((w)HR) = 1.09 (95% CI 1.02-1.16), p(trend) = 0.017; and n = 3,965, (w)HR = 1.04 (95% CI 0.94-1.16), p(trend) = 0.43; respectively. Subsequently, studies of MCF10A apicobasal polarization revealed a central role for BRCA1 and RHAMM, together with AURKA and TPX2, in essential reorganization of microtubules. Mechanistically, reorganization is facilitated by BRCA1 and impaired by AURKA, which is regulated by negative feedback involving RHAMM and TPX2. Taken together, our data provide fundamental insight into apicobasal polarization through BRCA1 function, which may explain the expanded cell subsets and characteristic tumor type accompanying BRCA1 mutation, while also linking this process to sporadic breast cancer through perturbation of HMMR/RHAMM.
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| 3. |
- Peltier, Aline, et al.
(författare)
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Volcano Crisis Management at Piton de la Fournaise (La Reunion) during the COVID-19 Lockdown
- 2021
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Ingår i: Seismological Research Letters. - : Seismological Society of America (SSA). - 1938-2057 .- 0895-0695. ; 92:1, s. 38-52
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Tidskriftsartikel (refereegranskat)abstract
- In March 2020, the coronavirus disease 2019 outbreak was declared a pandemic by the World Health Organization and became a global health crisis. Authorities worldwide implemented lockdowns to restrict travel and social exchanges in a global effort to counter the pandemic. In France, and in French overseas departments, the lockdown was effective from 17 March to 11 May 2020. It was in this context that the 2-6 April 2020 eruption of Piton de la Fournaise (La Reunion Island, Indian Ocean) took place. Upon the announcement of the lockdown in France, a reduced activity plan was set up by the Institut de Physique du Globe de Paris, which manages the Observatoire Volcanologique du Piton de la Fournaise (OVPF). The aim was to (1) maintain remote monitoring operations by teleworking and (2) authorize fieldwork only for critical reasons, such as serious breakdowns of stations or transmission relays. This eruption provided an opportunity for the observatory to validate its capacity to manage a volcanic crisis with 100% remotely operated monitoring networks. We thus present the longand short-term precursors to the eruption, and the evolution of the eruption recorded using the real-time monitoring data as communicated to the stakeholders. The data were from both continuously recording and transmitting field instruments as well as satellites. The volcano observatory staff remotely managed the volcano crisis with the various stakeholders based only on these remotely functioning networks. Monitoring duties were also assured in the absence of ad hoc field investigation of the eruption by observatory staff or face-to-face communications. The density and reliability of the OVPF networks, combined with satellite observations, allowed for trustworthy instrument-based monitoring of the eruption and continuity of the OVPF duties in issuing regular updates of volcanic activity in the context of a double crisis: volcanic and health.
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| 4. |
- Brunet, Jean-Philippe, et al.
(författare)
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All–to–All Broadcast with Applications on the Connection Machine
- 1992
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Ingår i: International Journal of Supercomputer Applications. ; 6:3, s. 241-256
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Tidskriftsartikel (refereegranskat)abstract
- An all-to-all broadcast algorithm that exploits concur rent communication on all channels of the Connection Machine system CM-200 binary cube network is de scribed. Issues in integrating a physical all-to-all broad cast between processing nodes into a language envi ronment using a global address space are discussed. Timings for the physical broadcast between nodes and for the virtual broadcast are given. The peak data transfer rate for the physical broadcast on a CM-200 is 5.9 gigabytes/sec, and the peak rate for the virtual broadcast is 31 gigabytes/sec. Array reshaping is an effective performance optimization technique. An ex ample is given where reshaping improved perfor mance by a factor of 7 by reducing the amount of local data motion. We also show how to exploit symmetry for computation of an interaction matrix using the all- to-all broadcast function. Further optimizations are suggested for N-body-type calculations. Using the all- to-all broadcast function, a peak rate of 9.3 GFLOPS/ sec has been achieved for the N-body computations in 32-bit precision on a 2,048 node Connection Machine system CM-200.
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| 5. |
- Brunet, Philippe, et al.
(författare)
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Defects and spatiotemporal disorder in a pattern of falling liquid columns
- 2004
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Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics. - 1063-651X .- 1095-3787. ; 70:4, s. 046207-
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Tidskriftsartikel (refereegranskat)abstract
- Disordered regimes of a one-dimensional pattern of liquid columns hanging below an overflowing circular dish are investigated experimentally. The interaction of two basic dynamical modes (oscillations and drift) combined with the occurrence of defects (birth of new columns, disappearances by coalescences of two columns) leads to spatiotemporal chaos. When the flow rate is progressively increased, a continuous transition between transient and permanent chaos is pointed into evidence. We introduce the rate of defects as the sole relevant quantity to quantify this "turbulence" without ambiguity. Statistics on both transient and endlessly chaotic regimes enable to define a critical flow rate around which exponents are extracted. Comparisons are drawn with other interfacial pattern-forming systems, where transition towards chaos follows similar steps. Qualitatively, careful examinations of the global dynamics show that the contamination processes are nonlocal and involve the propagation of blocks of elementary laminar states (such as propagative domains or local oscillations), emitted near the defects, which turn out to be essential ingredients of this self-sustained disorder.
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| 6. |
- Brunet, Philippe
(författare)
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Stabilized Kuramoto-Sivashinsky equation : A useful model for secondary instabilities and related dynamics of experimental one-dimensional cellular flows
- 2007
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Ingår i: PHYSICAL REVIEW E. - 1539-3755. ; 76:1, s. 017204-
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Tidskriftsartikel (refereegranskat)abstract
- We report numerical simulations of one-dimensional cellular solutions of the stabilized Kuramoto-Sivashinsky equation. This equation offers a range of generic behavior in pattern-forming instabilities of moving interfaces, such as a host of secondary instabilities or transition toward disorder. We compare some of these collective behaviors to those observed in experiments. In particular, destabilization scenarios of bifurcated states are studied in a spatially semi-extended situation, which is common in realistic patterns, but has been barely explored so far.
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| 7. |
- Hudson, Lawrence N, et al.
(författare)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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Ingår i: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Tidskriftsartikel (refereegranskat)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 8. |
- Hudson, Lawrence N., et al.
(författare)
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The PREDICTS database : a global database of how local terrestrial biodiversity responds to human impacts
- 2014
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Ingår i: Ecology and Evolution. - : Wiley. - 2045-7758. ; 4:24, s. 4701-4735
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Tidskriftsartikel (refereegranskat)abstract
- Biodiversity continues to decline in the face of increasing anthropogenic pressures such as habitat destruction, exploitation, pollution and introduction of alien species. Existing global databases of species' threat status or population time series are dominated by charismatic species. The collation of datasets with broad taxonomic and biogeographic extents, and that support computation of a range of biodiversity indicators, is necessary to enable better understanding of historical declines and to project - and avert - future declines. We describe and assess a new database of more than 1.6 million samples from 78 countries representing over 28,000 species, collated from existing spatial comparisons of local-scale biodiversity exposed to different intensities and types of anthropogenic pressures, from terrestrial sites around the world. The database contains measurements taken in 208 (of 814) ecoregions, 13 (of 14) biomes, 25 (of 35) biodiversity hotspots and 16 (of 17) megadiverse countries. The database contains more than 1% of the total number of all species described, and more than 1% of the described species within many taxonomic groups - including flowering plants, gymnosperms, birds, mammals, reptiles, amphibians, beetles, lepidopterans and hymenopterans. The dataset, which is still being added to, is therefore already considerably larger and more representative than those used by previous quantitative models of biodiversity trends and responses. The database is being assembled as part of the PREDICTS project (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems - ). We make site-level summary data available alongside this article. The full database will be publicly available in 2015.
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| 9. |
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| 10. |
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| 11. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 12. |
- Vanholder, Raymond, et al.
(författare)
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A bench to bedside view of uremic toxins.
- 2008
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Ingår i: Journal of the American Society of Nephrology : JASN. - 1533-3450. ; 19:5, s. 863-70
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Tidskriftsartikel (refereegranskat)abstract
- Reviewing the current picture of uremic toxicity reveals its complexity. Focusing on cardiovascular damage as a model of uremic effects resulting in substantial morbidity and mortality, most molecules with potential to affect the function of a variety of cell types within the vascular system are difficult to remove by dialysis. Examples are the larger middle molecular weight molecules and protein-bound molecules. Recent clinical studies suggest that enhancing the removal of these compounds is beneficial for survival. Future therapeutic options are discussed, including improved removal of toxins and the search for pharmacologic strategies blocking responsible pathophysiologic pathways.
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| 13. |
- Vanholder, Raymond, et al.
(författare)
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Conservative treatment of the uremic syndrome.
- 2009
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Ingår i: Seminars in dialysis. - 0894-0959 .- 1525-139X. ; 22:4, s. 449-453
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Tidskriftsartikel (refereegranskat)abstract
- In addition to extracorporeal renal replacement strategies, which in chronic kidney disease (CKD) are largely reserved for the treatment of end-stage kidney failure, conservative measures can be taken to reduce concentration, effects, or both concentration and effects of uremic retention solutes. In this overview, we will focus on those therapies, which are aimed at preventing or delaying cardio-vascular disease, retarding or halting the progression of CKD, or both. We will discuss, consecutively, inhibitors of the renin-angiotensin-aldosterone axis, beta-blockers, calcium-channel antagonists, anti-inflammatory drugs, intestinal sorbents, calcimimetics, and glitazones. Some of these approaches could lead to a therapeutic breakthrough in the future. In addition, comprehensive tables will be provided for more traditional therapeutic approaches, such as lifestyle changes and other pharmaceutical treatments.
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| 14. |
- Vanholder, Raymond, et al.
(författare)
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The role of EUTox in uremic toxin research.
- 2009
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Ingår i: Seminars in dialysis. - 0894-0959 .- 1525-139X. ; 22:4, s. 323-328
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Tidskriftsartikel (refereegranskat)abstract
- In this publication, we review the activities of the European Uremic Toxin Work Group (EUTox) in the field of uremic toxin research. Founded in 1999 under the umbrella of the European Society of Artificial Organs (ESAO), and active since 2000, this group focuses essentially on questions related to solute retention and removal during chronic kidney disease, and on the deleterious impact of those solutes on biological/biochemical systems. As of January 1, 2009, the group had met 28 times; it organized the third meeting, "Uremic Toxins in Cardiovascular Disease," which took place in October 2008 in Amiens, France. The current group is composed of 25 members belonging to 23 European research institutions. As of November 1, 2008, in total 69 papers had been published to which at least two different research groups belonging to EUTox have contributed in a collaborative effort. Of these, 40 papers were on original research and eight were specific EUTox reviews or position statements. A website (http://www.eutox.info) summarizes all relevant information concerning the work group. EUTox also developed an interactive uremic toxin database, where concentrations of known toxins are displayed, to be used by researchers in the field. In the future, EUTox intends to continue its focus on bench to bedside research with specific consideration of proteomics, metabonomics, secretomics, and genomics.
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