The anterior and intermediate lobes of the pituitary gland derive from the surface ectoderm. They provide a simple system to assess mechanisms of developmental identity established by tissue determinants. Each lobe contains a lineage expressing the hormone precursor pro-opiomelanocortin (POMC): the corticotropes and melanotropes. The T-box transcription factor Tpit controls terminal differentiation of both lineages. We now report on the unique role of Pax7 as a selector of intermediate lobe and melanotrope identity. Inactivation of the Pax7 gene results in loss of melanotrope gene expression and derepression of corticotrope genes. Pax7 acts by remodeling chromatin and allowing Tpit binding to a new subset of enhancers for activation of melanotrope-specific genes. Thus, the selector function of Pax7 is exerted through pioneer transcription factor activity. Genome-wide, the Pax7 pioneer activity is preferentially associated with composite binding sites that include paired and homeodomain motifs. Pax7 expression is conserved in human and dog melanotropes and defines two subtypes of pituitary adenomas causing Cushing's disease. In summary, expression of Pax7 provides a unique tissue identity to the pituitary intermediate lobe that alters Tpit-driven differentiation through pioneer and classical transcription factor activities.

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The roles of interleukin-17 (IL-17) and neutrophils in the lung have been described as those of two intricate but independent players. Here we identify neutrophils as the primary IL-17-secreting subset of cells in a model of inhalation anthrax using A/J and C57BL/6 mice. With IL-17 receptor A knockout (IL-17RA ؊/؊ ) mice, we confirmed that IL-17A/F signaling is instrumental in the self-recruitment of this population. We also show that the IL-17A/F axis is critical for surviving pulmonary infection, as IL-17RA ؊/؊ mice become susceptible to intranasal infection by Bacillus anthracis Sterne spores. Strikingly, infection with a fully virulent strain did not affect IL-17RA ؊/؊ mouse survival. Eventually, by depleting neutrophils in wild-type and IL-17RA ؊/؊ mice, we demonstrated the crucial role of IL-17-secreting neutrophils in mouse survival of infection by fully virulent B. anthracis. This work demonstrates the important roles of both IL-17 signaling and neutrophils in clearing this pathogen and surviving pulmonary B. anthracis infection.

Discrimination of Burkholderia (B.) pseudomallei and B. mallei from environmental B. thailandensis is challenging. We describe a discrimination method based on sequence comparison of the ribosomal protein S21 (rpsU) gene. The rpsU gene was sequenced in ten B. pseudomallei, six B. mallei, one B. thailandensis reference strains, six isolates of B. pseudomallei, and 37 of B. thailandensis. Further rpsU sequences of six B. pseudomallei, three B. mallei, and one B. thailandensis were identified via NCBI GenBank. Three to four variable base-positions were identified within a 120-base-pair fragment, allowing discrimination of the B. pseudomallei/mallei-cluster from B. thailandensis, whose sequences clustered identically. All B. mallei and three B. pseudomallei sequences were identical, while 17/22 B. pseudomallei strains differed in one nucleotide (78A>C). Sequences of the rpsU fragment of ‘out-stander’ reference strains of B. cepacia, B. gladioli, B. plantarii, and B. vietnamensis clustered differently. Sequence comparison of the described rpsU gene fragment can be used as a supplementary diagnostic procedure for the discrimination of B. mallei/pseudomallei from B. thailandensis as well as from other species of the genus Burkholderia, keeping in mind that it does not allow for a differentiation between B. mallei and B. pseudomallei.

This article takes a human rights perspective with a view to articulating the infant’s perspective when the infant has been subjected to abuse, neglect, or both and is reliant on the state to ensure his or her health and well-being. When a young child is removed from parental care, important and often difficult decisions have to be made about subsequent contact between child and parent. We consider a number of dilemmas which may arise for practitioners when they are assisting child welfare decision makers in relation to contact, and acknowledge the limited empirical follow-up studies of the impact of child welfare practice and legal decisions on infant outcomes. We draw on the significant and substantive evidence base about infant emotional and cognitive development and infant–parent attachment relationships as well as infant mental health to illuminate the infant’s subjective experience in these practice dilemmas. We describe innovations in practice from various countries, which seek to shed light on the challenges often associated with contact.

In the framework of the IFMIF-EVEDA project (International Fusion Materials Irradiation Facility-Engineering Validation and Engineering Design Activities), CEA∕IRFU is in charge of the design, construction, and characterization of the 140 mA continuous deuteron injector, including the source and the low energy beam line. The electron cyclotron resonance ion source which operates at 2.45 GHz is associated with a 4-electrode extraction system in order to minimize beam divergence at the source exit. Krypton gas injection is foreseen in the 2-solenoid low energy beam line. Such Kr injection will allow reaching a high level of space charge compensation in order to improve the beam matching at the radio frequency quadrupole (RFQ) entrance. The injector construction is now completed on the Saclay site and the first plasma and beam production has been produced in May 2011. This installation will be tested with proton and deuteron beams either in pulsed or continuous mode at Saclay before shipping to Japan. In this paper, after a brief description of the installation, the preliminary results obtained with hydrogen gas injection into the plasma chamber will be reported.

The production of rare radioactive ion beam (RIB) far from the valley of stability is one of the final purposes of the Spiral2 facility in Caen. The RIB will be produced by impinging a deuteron beam onto a carbon sample to produce a high neutron flux, which will interact with a uranium target. The primary deuteron beam is produced by an ion source based on ECR plasma generation. The deuteron source and the low energy beam transport (LEBT) has been assembled and tested at CEA Saclay. Diagnostics from other laboratories were implemented on the LEBT in order to characterize the deuteron beam produced and compare it to the initial simulations. The ion source has been based on a SILHI-type source, which has demonstrated good performances in pulsed and continuous mode, and also a very good reliability on long term operation. The 5 mA of deuteron beam required at the RFQ entrance is extracted from the plasma source at the energy of 40 kV. After a brief description of the experimental set-up, this article reports on the first beam characterization experiments.

The prevalence of autoimmune atrophic gastritis (AAG) in vitiligo patients was estimated at about 15%. In both conditions, a release of specific antibodies and an autoimmune destruction of target cells (melanocytes in vitiligo, parietal cells (PC) in AAG) mediated by CD8‐T lymphocytes was demonstrated to perform a comparative histological study of vitiligo skin and AAG mucosa. In two patients with concomitant vitiligo and AAG, biopsies from the vitiligo lesions and gastric mucosa from corpus fundus were performed. Sections were immunostained with E‐cadherin, Coll IV, CD8, CD20, CD4 antibodies. The skin sections also were stained with HES, HMB45, MITF. Common histological findings were found in both diseases. Adhesivity impairment with down expression of E‐cadherin and Coll IV was objectivated. The protruding MITF+melanocytes and the detached PC were surrounded by an infiltrate including CD8 and CD4. CD8 was infiltrating the epidermis in close contact with the remaining melanocytes and the gastric glands around the remaining PC. In both diseases, the autoimmune process could be preceded by a detachment of either melanocytes in vitiligo or PC in AAG possibly in relation to an initial adhesivity impairment of these cells. Common autoimmune mechanisms could be suggested for both diseases.