466 research outputs found
Human proliferating cell nuclear antigen, poly(ADP-ribose) polymerase-1, and p21waf1/cip1. A dynamic exchange of partners.
We addressed the analysis of the physical and functional association of proliferating cell nuclear antigen (PCNA), a protein involved in many DNA transactions, with poly(ADP-ribose) polymerase (PARP-1), an enzyme that plays a crucial role in DNA repair and interacts with many DNA replication/repair factors. We demonstrated that PARP-1 and PCNA co-immunoprecipitated both from the soluble and the DNA-bound fraction isolated from S-phase-synchronized HeLa cells. Immunoprecipitation experiments with purified proteins further confirmed a physical association between PARP-1 and PCNA. To investigate the effect of this association on PARP-1 activity, an assay based on the incorporation of radioactive NAD was performed. Conversely, the effect of PARP-1 on PCNA-dependent DNA synthesis was assessed by a DNA polymerase delta assay. A marked inhibition of both reactions was found. Unexpectedly, PARP-1 activity also decreased in the presence of p21waf1/cip1. By pull-down experiments, we provided the first evidence for an association between PARP-1 and p21, which involves the C-terminal part of p21 protein. This association was further demonstrated to occur also in vivo in MNNG (N-methyl-N'-nitro-N-nitrosoguanidine)-treated human fibroblasts. These observations suggest that PARP-1 and p21 could cooperate in regulating the functions of PCNA during DNA replication/repair
Genetic variations within human gained enhancer elements affect human brain sulcal morphology.
The expansion of the cerebral cortex is one of the most distinctive changes in the evolution of the human brain. Cortical expansion and related increases in cortical folding may have contributed to emergence of our capacities for high-order cognitive abilities. Molecular analysis of humans, archaic hominins, and non-human primates has allowed identification of chromosomal regions showing evolutionary changes at different points of our phylogenetic history. In this study, we assessed the contributions of genomic annotations spanning 30 million years to human sulcal morphology measured via MRI in more than 18,000 participants from the UK Biobank. We found that variation within brain-expressed human gained enhancers, regulatory genetic elements that emerged since our last common ancestor with Old World monkeys, explained more trait heritability than expected for the left and right calloso-marginal posterior fissures and the right central sulcus. Intriguingly, these are sulci that have been previously linked to the evolution of locomotion in primates and later on bipedalism in our hominin ancestors
A mutual reference shape based on information theory
International audienceIn this paper, we propose to consider the estimation of a refer-ence shape from a set of different segmentation results using both active contours and information theory. The reference shape is defined as the minimum of a criterion that benefits from both the mutual information and the joint entropy of the input segmentations and called a mutual shape. This energy criterion is here justified using similarities between informa-tion theory quantities and area measures, and presented in a continuous variational framework. This framework brings out some interesting evaluation measures such as the speci-ficity and sensitivity. In order to solve this shape optimization problem, shape derivatives are computed for each term of the criterion and interpreted as an evolution equation of an active contour. Some synthetical examples allow us to cast the light on the difference between our mutual shape and an average shape. Our framework has been considered for the estimation of a mutual shape for the evaluation of cardiac segmentation methods in MRI
Modeling Atmosphere-Ocean Radiative Transfer: A PACE Mission Perspective
The research frontiers of radiative transfer (RT) in coupled atmosphere-ocean systems are explored to enable new science and specifically to support the upcoming Plankton, Aerosol, Cloud ocean Ecosystem (PACE) satellite mission. Given (i) the multitude of atmospheric and oceanic constituents at any given moment that each exhibits a large variety of physical and chemical properties and (ii) the diversity of light-matter interactions (scattering, absorption, and emission), tackling all outstanding RT aspects related to interpreting and/or simulating light reflected by atmosphere-ocean systems becomes impossible. Instead, we focus on both theoretical and experimental studies of RT topics important to the science threshold and goal questions of the PACE mission and the measurement capabilities of its instruments. We differentiate between (a) forward (FWD) RT studies that focus mainly on sensitivity to influencing variables and/or simulating data sets, and (b) inverse (INV) RT studies that also involve the retrieval of atmosphere and ocean parameters. Our topics cover (1) the ocean (i.e., water body): absorption and elastic/inelastic scattering by pure water (FWD RT) and models for scattering and absorption by particulates (FWD RT and INV RT); (2) the air-water interface: variations in ocean surface refractive index (INV RT) and in whitecap reflectance (INV RT); (3) the atmosphere: polarimetric and/or hyperspectral remote sensing of aerosols (INV RT) and of gases (FWD RT); and (4) atmosphere-ocean systems: benchmark comparisons, impact of the Earth's sphericity and adjacency effects on space-borne observations, and scattering in the ultraviolet regime (FWD RT). We provide for each topic a summary of past relevant (heritage) work, followed by a discussion (for unresolved questions) and RT updates
Modeling atmosphere-ocean radiative transfer: A PACE mission perspective
The research frontiers of radiative transfer (RT) in coupled atmosphere-ocean systems are explored to enable new science and specifically to support the upcoming Plankton, Aerosol, Cloud ocean Ecosystem (PACE) satellite mission. Given (i) the multitude of atmospheric and oceanic constituents at any given moment that each exhibits a large variety of physical and chemical properties and (ii) the diversity of light-matter interactions (scattering, absorption, and emission), tackling all outstanding RT aspects related to interpreting and/or simulating light reflected by atmosphere-ocean systems becomes impossible. Instead, we focus on both theoretical and experimental studies of RT topics important to the science threshold and goal questions of the PACE mission and the measurement capabilities of its instruments. We differentiate between (a) forward (FWD) RT studies that focus mainly on sensitivity to influencing variables and/or simulating data sets, and (b) inverse (INV) RT studies that also involve the retrieval of atmosphere and ocean parameters. Our topics cover (1) the ocean (i.e., water body): absorption and elastic/inelastic scattering by pure water (FWD RT) and models for scattering and absorption by particulates (FWD RT and INV RT); (2) the air-water interface: variations in ocean surface refractive index (INV RT) and in whitecap reflectance (INV RT); (3) the atmosphere: polarimetric and/or hyperspectral remote sensing of aerosols (INV RT) and of gases (FWD RT); and (4) atmosphere-ocean systems: benchmark comparisons, impact of the Earth’s sphericity and adjacency effects on space-borne observations, and scattering in the ultraviolet regime (FWD RT). We provide for each topic a summary of past relevant (heritage) work, followed by a discussion (for unresolved questions) and RT updates
Modeling Atmosphere-Ocean Radiative Transfer: A PACE Mission Perspective
The research frontiers of radiative transfer (RT) in coupled atmosphere-ocean systems are explored to enable new science and specifically to support the upcoming Plankton, Aerosol, Cloud ocean Ecosystem (PACE) satellite mission. Given (i) the multitude of atmospheric and oceanic constituents at any given moment that each exhibits a large variety of physical and chemical properties and (ii) the diversity of light-matter interactions (scattering, absorption, and emission), tackling all outstanding RT aspects related to interpreting and/or simulating light reflected by atmosphere-ocean systems becomes impossible. Instead, we focus on both theoretical and experimental studies of RT topics important to the science threshold and goal questions of the PACE mission and the measurement capabilities of its instruments. We differentiate between (a) forward (FWD) RT studies that focus mainly on sensitivity to influencing variables and/or simulating data sets, and (b) inverse (INV) RT studies that also involve the retrieval of atmosphere and ocean parameters. Our topics cover (1) the ocean (i.e., water body): absorption and elastic/inelastic scattering by pure water (FWD RT) and models for scattering and absorption by particulates (FWD RT and INV RT); (2) the air-water interface: variations in ocean surface refractive index (INV RT) and in whitecap reflectance (INV RT); (3) the atmosphere: polarimetric and/or hyperspectral remote sensing of aerosols (INV RT) and of gases (FWD RT); and (4) atmosphere-ocean systems: benchmark comparisons, impact of the Earth’s sphericity and adjacency effects on space-borne observations, and scattering in the ultraviolet regime (FWD RT). We provide for each topic a summary of past relevant (heritage) work, followed by a discussion (for unresolved questions) and RT updates
Gigwa v2—Extended and improved genotype investigator
The study of genetic variations is the basis of many research domains in biology. From genome structure to population dynamics, many applications involve the use of genetic variants. The advent of next-generation sequencing technologies led to such a flood of data that the daily work of scientists is often more focused on data management than data analysis. This mass of genotyping data poses several computational challenges in terms of storage, search, sharing, analysis, and visualization. While existing tools try to solve these challenges, few of them offer a comprehensive and scalable solution.
Gigwa v2 is an easy-to-use, species-agnostic web application for managing and exploring high-density genotyping data. It can handle multiple databases and may be installed on a local computer or deployed as an online data portal. It supports various standard import and export formats, provides advanced filtering options, and offers means to visualize density charts or push selected data into various stand-alone or online tools. It implements 2 standard RESTful application programming interfaces, GA4GH, which is health-oriented, and BrAPI, which is breeding-oriented, thus offering wide possibilities of interaction with third-party applications. The project home page provides a list of live instances allowing users to test the system on public data (or reasonably sized user-provided data).
This new version of Gigwa provides a more intuitive and more powerful way to explore large amounts of genotyping data by offering a scalable solution to search for genotype patterns, functional annotations, or more complex filtering. Furthermore, its user-friendliness and interoperability make it widely accessible to the life science community
Seagrass macroinvertebrate bycatches support mosquito net trawl fishery in Madagascar
The use of mosquito nets, primarily for targeting small and/or juvenile fish, has rapidly increased in Western Indian Ocean shallow seagrass beds and coral reefs over the last 20 years. However, to date, invertebrate by-catch by locally-made fishing gear has not been reported. We studied the mosquito net trawl fishery in seagrass areas in the Bay of Toliara, Southwest Madagascar through the GPS tracking of fishers from August 2018 to February 2019. Catches were monitored through monthly landing surveys to characterize spatial temporal patterns in the abundance and diversity of macroinvertebrates in the seagrass beds. Fishing was carried out at low tide, mostly at night, by fishers pulling a hand-made trawl net of varying dimensions. Overall, 43 macroinvertebrate taxa were identified out of 217,080 individuals collected from 109 catch samples. Catches were generally composed of crustaceans (mainly Portunidae, Processidae, Penaeidae, and Alpheidae). The crab Thalamita mitsiensis largely dominated the abundance and biomass of the macroinvertebrate assemblage (from 6% to 100% and from 5 to 100% of the overall density and biomass, respectively). Macroinvertebrates composed 1.5% to 100% of the total catch per trip (i.e., 4–55 kg trip−1). They were sold for human consumption or animal feed, which provided additional income to fishers (USD 1–24 trip−1 and 1–72% of catch income per trip). This study revealed that macroinvertebrate resources provide valuable by-catch to small-scale fishers in Southwest Madagascar. This bycatch generates income that further encourages the use of mosquito net trawls and exacerbates their negative effects on coastal seagrass ecosystems and fisheries
Cytokine Signature in Schnitzler Syndrome: Proinflammatory Cytokine Production Associated to Th Suppression
Background: Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal IgM gammopathy. Overactivation of the interleukin(IL)-1 system is reported, even though the exact pathophysiological pathways remain unknown. Objective: To determine ex vivo cytokine profiles of Peripheral Blood Mononuclear Cells (PBMCs) from SchS patients prior to treatment and after initiation of anti-IL-1 therapy (anakinra). The sera cytokine profile was studied in parallel. Methods: We collected blood samples from thirty-six untreated or treated SchS. PBMCs were cultured with and without LPS or anti-CD3/CD28. Cytokine levels were evaluated in serum and cell culture supernatants using Luminex technology. Results: Spontaneous TNFα, IL-6, IL-1β, IL-1α, and IL-1RA release by PBMCs of SchS patients were higher than in controls. LPS-stimulation further induced the secretion of these cytokines. In contrast, after T-cell stimulation, TNFα, IL-10, IFNγ, IL-17A, and IL-4 production decreased in SchS patients compared to healthy controls, but less in treated patients. Whereas IL-1β serum level was not detected in most sera, IL-6, IL-10, and TNFα serum levels were higher in patients with SchS and IFNγ and IL-4 levels were lower. Of note, IL-6 decreased after treatment in SchS (p = 0.04). Conclusion: Our data strengthen the hypothesis of myeloid inflammation in SchS, mediated in particular by IL-1β, TNFα, and IL-6, associated with overproduction of the inhibitors IL-1RA and IL-10. In contrast, we observed a loss of Th1, Th2, and Th17 cell functionalities that tends to be reversed by anakinra
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