Irradiation-Induced Deinococcus radiodurans Genome Fragmentation Triggers Transposition of a Single Resident Insertion Sequence

Stress-induced transposition is an attractive notion since it is potentially important in creating diversity to facilitate adaptation of the host to severe environmental conditions. One common major stress is radiation-induced DNA damage. Deinococcus radiodurans has an exceptional ability to withstand the lethal effects of DNA–damaging agents (ionizing radiation, UV light, and desiccation). High radiation levels result in genome fragmentation and reassembly in a process which generates significant amounts of single-stranded DNA. This capacity of D. radiodurans to withstand irradiation raises important questions concerning its response to radiation-induced mutagenic lesions. A recent study analyzed the mutational profile in the thyA gene following irradiation. The majority of thyA mutants resulted from transposition of one particular Insertion Sequence (IS), ISDra2, of the many different ISs in the D. radiodurans genome. ISDra2 is a member of a newly recognised class of ISs, the IS200/IS605 family of insertion sequences

A Major Role of the RecFOR Pathway in DNA Double-Strand-Break Repair through ESDSA in Deinococcus radiodurans

In Deinococcus radiodurans, the extreme resistance to DNA–shattering treatments such as ionizing radiation or desiccation is correlated with its ability to reconstruct a functional genome from hundreds of chromosomal fragments. The rapid reconstitution of an intact genome is thought to occur through an extended synthesis-dependent strand annealing process (ESDSA) followed by DNA recombination. Here, we investigated the role of key components of the RecF pathway in ESDSA in this organism naturally devoid of RecB and RecC proteins. We demonstrate that inactivation of RecJ exonuclease results in cell lethality, indicating that this protein plays a key role in genome maintenance. Cells devoid of RecF, RecO, or RecR proteins also display greatly impaired growth and an important lethal sectoring as bacteria devoid of RecA protein. Other aspects of the phenotype of recFOR knock-out mutants paralleled that of a ΔrecA mutant: ΔrecFOR mutants are extremely radiosensitive and show a slow assembly of radiation-induced chromosomal fragments, not accompanied by DNA synthesis, and reduced DNA degradation. Cells devoid of RecQ, the major helicase implicated in repair through the RecF pathway in E. coli, are resistant to γ-irradiation and have a wild-type DNA repair capacity as also shown for cells devoid of the RecD helicase; in contrast, ΔuvrD mutants show a markedly decreased radioresistance, an increased latent period in the kinetics of DNA double-strand-break repair, and a slow rate of fragment assembly correlated with a slow rate of DNA synthesis. Combining RecQ or RecD deficiency with UvrD deficiency did not significantly accentuate the phenotype of ΔuvrD mutants. In conclusion, RecFOR proteins are essential for DNA double-strand-break repair through ESDSA whereas RecJ protein is essential for cell viability and UvrD helicase might be involved in the processing of double stranded DNA ends and/or in the DNA synthesis step of ESDSA

Disability Policies in France: Changes and Tensions between the Category-based, Universalist and Personalized Approaches

In this article, the authors show that the current French disability policy is traversed by conflicts between three different approaches to disability which came about at different periods in history. They begin by looking at the origins of disability policy in France. This policy was developed during the 20th century, from notions of repair, indemnification and compensation through rehabilitation. It became institutionalized in 1975, when two laws were passed, giving it the form of a category-based policy. Between 1970 and 2000, affected by the international situation, this policy came into conflict with a universalist policy. More recently there has been a desire to develop a personalized approach. Finally, the authors use two examples (taken from recent debates on the implementation in France of the new law of 11 February 2005) to show the tensions that have led to the coexistence of these three approaches within current disability policy

Applications of imaging methodologies to paleoanthropology : beneficial results relating to the preservation, management and development of collections

The limited number of unearthed fossils and their accessibility are factors that hinder paleoanthropological studies. Original remains, but also osteological collections of extant specimens, have to be curated in optimal and adapted environments, and direct manipulation needs to be limited in order to preserve this irreplaceable patrimony. Imaging methodologies have recently provided ways for innovative advances in the preservation of these collections, as well as offering new perspectives to museographic displays and original scientific studies. Here, we describe recent examples of developments obtained from imaging methodologies and discuss methodological and ethical implications of these new "virtual" collections. Undeniably, "virtual anthropology" is an additional tool in our large set of analytical possibilities and for curators, with its specific constraints related to the particular nature of the analysed material. Finally, we suggest some possible guidelines for the optimisation of the preservation, management and development of collections while preserving their scientific exploitation

Inhibiteurs du check-point immunitaire en néo-adjuvant dans les cancers bronchiques non à petites cellules localisés : Essai clinique de phase II IFCT-1601 IoNESCO

International audienceBackgroundProgrammed cell death-ligand 1 (PD-L1) is a checkpoint receptor that facilitates immune evasion by tumor cells, through interaction with programmed cell death-1 (PD-1), a receptor expressed by T-cells. Durvalumab is an anti-PD-L1 monoclonal antibody that blocks PD-L1 interaction with PD-1 on T-cells, countering the tumor's immune-evading tactics. Phase I/II studies demonstrated durable responses and manageable tolerability in heavily pre-treated patients with non-small cell lung cancer (NSCLC).MethodsThis phase II study is designed to administrate three durvalumab IV infusions (10 mg/kg at day 1, 15, 29) before surgery, to patients with pathologically confirmed NSCLC, clinical stage IB (> 4 cm) or stage II, ≥ 18 years of age, WHO performans status 0–1, without selection on PD-L1 expression. Preoperative chemotherapy and radiation therapy are not permitted. The primary objective is feasibility of complete surgical resection. Major pathological response on surgical tissue, defined as 10% or less remaining tumor cells, will be a secondary objective. Additional secondary objectives include tolerance, adverse effects, delay between start of treatment and surgery, response rate (RECIST 1.1), metabolic response rate, postoperative adverse events, disease-free survival and overall survival. A rate of complete resection 4 cm) ou II. La chimiothérapie et la radiothérapie préopératoire ne sont pas permises. L’objectif principal est la faisabilité d’une résection chirurgicale complète. Un taux de résection complète < 85 % (P0) est considéré comme inacceptable. Avec une hypothèse P1 de 95 %, une puissance de 90 % et un risque alpha de 5 %, 81 patients sont nécessaires. La réponse histologique majeure (≤ 10 % de cellules tumorales résiduelles sur la pièce opératoire) est un objectif secondaire. Les autres objectifs sont le délai entre traitement et chirurgie, les taux de réponse radiologique et métabolique, les évènements indésirables, la survie sans récidive et globale.Résultats attendusL’immunothérapie néo-adjuvante est faisable et pourrait améliorer la survie des CBNPC de stade précoce