Gene Expression during the Generation and Activation of Mouse Neutrophils: Implication of Novel Functional and Regulatory Pathways

As part of the Immunological Genome Project (ImmGen), gene expression was determined in unstimulated (circulating) mouse neutrophils and three populations of neutrophils activated in vivo, with comparison among these populations and to other leukocytes. Activation conditions included serum-transfer arthritis (mediated by immune complexes), thioglycollate-induced peritonitis, and uric acid-induced peritonitis. Neutrophils expressed fewer genes than any other leukocyte population studied in ImmGen, and down-regulation of genes related to translation was particularly striking. However, genes with expression relatively specific to neutrophils were also identified, particularly three genes of unknown function: Stfa2l1, Mrgpr2a and Mrgpr2b. Comparison of genes up-regulated in activated neutrophils led to several novel findings: increased expression of genes related to synthesis and use of glutathione and of genes related to uptake and metabolism of modified lipoproteins, particularly in neutrophils elicited by thioglycollate; increased expression of genes for transcription factors in the Nr4a family, only in neutrophils elicited by serum-transfer arthritis; and increased expression of genes important in synthesis of prostaglandins and response to leukotrienes, particularly in neutrophils elicited by uric acid. Up-regulation of genes related to apoptosis, response to microbial products, NFkB family members and their regulators, and MHC class II expression was also seen, in agreement with previous studies. A regulatory model developed from the ImmGen data was used to infer regulatory genes involved in the changes in gene expression during neutrophil activation. Among 64, mostly novel, regulatory genes predicted to influence these changes in gene expression, Irf5 was shown to be important for optimal secretion of IL-10, IP-10, MIP-1α, MIP-1β, and TNF-α by mouse neutrophils in vitro after stimulation through TLR9. This data-set and its analysis using the ImmGen regulatory model provide a basis for additional hypothesis-based research on the importance of changes in gene expression in neutrophils in different conditions

Does polycystic ovarian morphology influence the response to treatment with pulsatile GnRH in functional hypothalamic amenorrhea?

BACKGROUND: Pulsatile GnRH therapy is the gold standard treatment for ovulation induction in women having functional hypothalamic amenorrhea (FHA). The use of pulsatile GnRH therapy in FHA patients with polycystic ovarian morphology (PCOM), called “FHA-PCOM”, has been little studied in the literature and results remain contradictory. The aim of this study was to compare the outcomes of pulsatile GnRH therapy for ovulation induction between FHA and “FHA-PCOM” patients in order to search for an eventual impact of PCOM. METHODS: Retrospective study from August 2002 to June 2015, including 27 patients with FHA and 40 “FHA-PCOM” patients (85 and 104 initiated cycles, respectively) treated by pulsatile GnRH therapy for induction ovulation. RESULTS: The two groups were similar except for markers of PCOM (follicle number per ovary, serum Anti-Müllerian Hormone level and ovarian area), which were significantly higher in patients with “FHA-PCOM”. There was no significant difference between the groups concerning the ovarian response: with equivalent doses of GnRH, both groups had similar ovulation (80.8 vs 77.7 %, NS) and excessive response rates (12.5 vs 10.6 %, NS). There was no significant difference in on-going pregnancy rates (26.9 vs 20 % per initiated cycle, NS), as well as in miscarriage, multiple pregnancy or biochemical pregnancy rates. CONCLUSION: Pulsatile GnRH seems to be a successful and safe method for ovulation induction in “FHA-PCOM” patients. If results were confirmed by prospective studies, GnRH therapy could therefore become a first-line treatment for this specific population, just as it is for women with FHA without PCOM

Direct evidence for oscillatory screening in the quantum Hall effect regime

Oscillations of magneto-donor binding energies are observed in photoluminescence spectra of modulation-doped $\rm GaAs/Ga_{0.67}Al_{0.33}As$ heterostructure. Both the experiment and the underlying theory provide direct evidence for an oscillatory screening of the Coulomb interaction by two-dimensional electron gas in the quantum Hall effect regime

Pressure-induced disappearance of the local rhombohedral distortion in BaTiO3.

BaTiO has been studied by X-ray absorption spectroscopy at the Ti K edge up to 19GPa in a diamond anvil cell at room temperature. The pre-edge features observed at the Ti K edge are sensitive to the pressure. It is shown that the high-pressure cubic phase obtained above 2GPa is similar to the high-temperature one, with titanium out of the centre of the oxygen octahedron. Between 2 and 10GPa the intensity of the pre-edge features decreases indicating that the Ti atom is moving toward the centre of the oxygen octahedron. Above 10GPa, the features do not change anymore, showing that the Ti atom is at the centre of the oxygen octahedron. No correlation between the Ti atom position and the Raman activity under pressure is observed

High pressure x-ray absorption spectroscopy at lower energy in the dispersive mode: application to Ce and FePO4.

X-ray absorption spectroscopy (XAS) using a diamond anvil cell has been extended to lower energies (below 6 keV) thanks to smaller diamond anvils and to a new acquisition set-up on the energy dispersive x-ray absorption beamline of LURE. The valence change of Ce with pressure is followed at the LIII edge of cerium up to 8 GPa together with the bond length variation during the same experiment. The pressure induced coordination change around the Fe atom in FePO4 is determined at the Fe K edge through the pre-edge feature behaviour, the XANES modification and the Fe–O bond length increase

Expression of a dominant negative form of Daxx in vivo rescues motoneurons from Fas (CD95)-induced cell death

International audienceFas-induced death of motoneurons in vitro has been shown to involve two signaling cascades that act together to execute the death program: a Fas-Daxx-ASK-1-p38 kinase-nNOS branch, which controls transcriptional and post-translational events, and the second classical Fas-FADD-caspase-8 branch. To analyze the role of Daxx in the developmental motoneuron cell death, we studied Fas-dependent cell death in motoneurons from transgenic mice that overexpress a dominant-negative form of Daxx. Motoneurons purified from these transgenic mice are resistant to Fas-induced death. This protective effect is specific to Fas because ultraviolet irradiation-triggered death is not affected by the transgene. The Daxx and the FADD pathways work in parallel because only Daxx, but not FADD, is involved in the transcriptional control of neuronal nitric oxide synthase and nitric oxide production. Nevertheless, we do not observe involvement of Daxx in developmental motoneuronal cell death, as the pattern of naturally occurring programmed cell death in vivo is normal in transgenic mice overexpressing the dominant negative form of Daxx, suggesting that Daxx-independent pathways are used during development