Kinase and Phosphatase Cross-Talk at the Kinetochore

Multiple kinases and phosphatases act on the kinetochore to control chromosome segregation: Aurora B, Mps1, Bub1, Plk1, Cdk1, PP1, and PP2A-B56, have all been shown to regulate both kinetochore-microtubule attachments and the spindle assembly checkpoint. Given that so many kinases and phosphatases converge onto two key mitotic processes, it is perhaps not surprising to learn that they are, quite literally, entangled in cross-talk. Inhibition of any one of these enzymes produces secondary effects on all the others, which results in a complicated picture that is very difficult to interpret. This review aims to clarify this picture by first collating the direct effects of each enzyme into one overarching schematic of regulation at the Knl1/Mis12/Ndc80 (KMN) network (a major signaling hub at the outer kinetochore). This schematic will then be used to discuss the implications of the cross-talk that connects these enzymes; both in terms of why it may be needed to produce the right type of kinetochore signals and why it nevertheless complicates our interpretations about which enzymes control what processes. Finally, some general experimental approaches will be discussed that could help to characterize kinetochore signaling by dissociating the direct from indirect effect of kinase or phosphatase inhibition in vivo. Together, this review should provide a framework to help understand how a network of kinases and phosphatases cooperate to regulate two key mitotic processes

cfDNA Sequencing: Technological Approaches and Bioinformatic Issues

International audienceIn the era of precision medicine, it is crucial to identify molecular alterations that will guide the therapeutic management of patients. In this context, circulating tumoral DNA (ctDNA) released by the tumor in body fluids, like blood, and carrying its molecular characteristics is becoming a powerful biomarker for non-invasive detection and monitoring of cancer. Major recent technological advances, especially in terms of sequencing, have made possible its analysis, the challenge still being its reliable early detection. Different parameters, from the pre-analytical phase to the choice of sequencing technology and bioinformatic tools can influence the sensitivity of ctDNA detection

Dans les remous de la mémoire / Yvon Bohers

Collection : Collection Chemins profonds ; 95Contient une table des matièresAvec mode text

Study of Consumer Preferences of Regional Labeling. Slovak Case Study

The authors of the article consider regional labeling as a marketing tool which can contribute to the development of regional activities. These are focused mainly on traditional regional products and products. Their general popularity in prosperous regions is an important source of income for the inhabitants. In the less developed regions, it represents a significant stimulating tool of development. By means of a Slovak region of Gemer-Malohont as an example, the authors bring quantitative findings related to the preference of regional brands. They took into consideration the indicators of age, gender, education, monthly income and locality in connection with preference of regional products. They pointed to the fact that regional labeling has a mobilizing function to link and then jointly present its local activities. The behaviour of the population from the regions is an important recommendation for small producers and producers from less developed regions of Central Europe

Absence of transmission of vYF next generation Yellow Fever vaccine in mosquitoes

International audienceOne of the most effective vaccines against an arbovirus is the YFV-17D live-attenuated vaccine developed in 1937 against Yellow Fever (YF). This vaccine replicates poorly in mosquitoes and consequently, is not transmitted by vectors. Vaccine shortages, mainly due to constrained productions based on pathogen-free embryonated eggs, led Sanofi to move towards alternative methods based on a state-of-the-art process using continuous cell line cultures in bioreactor. vYF-247 is a next-generation live-attenuated vaccine candidate based on 17D adapted to grow in serum-free Vero cells. For the development of a new vaccine, WHO recommends to document infectivity and replication in mosquitoes. Here we infected Aedes aegypti and Aedes albopictus mosquitoes with vYF-247 vaccine compared first to the YF-17D-204 reference Sanofi vaccines (Stamaril and YF-VAX) and a clinical human isolate S-79, provided in a blood meal at a titer of 6.5 Log ffu/mL and secondly, to the clinical isolate only at an increased titer of 7.5 Log ffu/mL. At different days post-infection, virus replication, dissemination and transmission were evaluated by quantifying viral particles in mosquito abdomen, head and thorax or saliva, respectively. Although comparison of vYF-247 to reference vaccines could not be completed to yield significant results, we showed that vYF-247 was not transmitted by both Aedes species, either laboratory strains or field-collected populations, compared to clinical strain S-79 at the highest inoculation dose. Combined with the undetectable to low level viremia detected in vaccinees, transmission of the vYF-247 vaccine by mosquitoes is highly unlikely