Evidence for impurity-induced frustration in La2CuO4

Zero-field muon spin rotation and magnetization measurements were performed in La2Cu{1-x}MxO4, for 0<x< 0.12, where Cu2+ is replaced either by M=Zn2+ or by M=Mg2+ spinless impurity. It is shown that while the doping dependence of the sublattice magnetization (M(x)) is nearly the same for both compounds, the N\'eel temperature (T_N(x)) decreases unambiguously more rapidly in the Zn-doped compound. This difference, not taken into account within a simple dilution model, is associated with the frustration induced by the Zn2+ impurity onto the Cu2+ antiferromagnetic lattice. In fact, from T_N(x) and M(x) the spin stiffness is derived and found to be reduced by Zn doping more significantly than expected within a dilution model. The effect of the structural modifications induced by doping on the exchange coupling is also discussed.Comment: 4 pages, 4 figure

Experimental evidence that a high electric field acts as an efficient external parameter during crystalline growth of bulk oxide

International audienceA new crystal growth device, in which a high static external electric voltage (up to 14 kV) is added to a floating zone method, is described. Our first experiments show that the application of such an electric field acts like an external force, introducing a pressure effect which is in direct competition with temperature in the solid/liquid thermodynamic equilibrium. High electric fields could therefore be an additional parameter in crystal growth, opening original routes to the synthesis of new materials

Liquid chromatography-tandem mass spectrometry (LC/APCI-MS/MS) methods for the quantification of captan and folpet phthalimide metabolites in human plasma and urine.

Captan and folpet are fungicides largely used in agriculture. They have similar chemical structures, except that folpet has an aromatic ring unlike captan. Their half-lives in blood are very short, given that they are readily broken down to tetrahydrophthalimide (THPI) and phthalimide (PI), respectively. Few authors measured these biomarkers in plasma or urine, and analysis was conducted either by gas chromatography coupled to mass spectrometry or liquid chromatography with UV detection. The objective of this study was thus to develop simple, sensitive and specific liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry (LC/APCI-MS/MS) methods to quantify both THPI and PI in human plasma and urine. Briefly, deuterated THPI was added as an internal standard and purification was performed by solid-phase extraction followed by LC/APCI-MS/MS analysis in negative ion mode for both compounds. Validation of the methods was conducted using spiked blank plasma and urine samples at concentrations ranging from 1 to 250 μg/L and 1 to 50 μg/L, respectively, along with samples of volunteers and workers exposed to captan or folpet. The methods showed a good linearity (R (2) &gt; 0.99), recovery (on average 90% for THPI and 75% for PI), intra- and inter-day precision (RSD, &lt;15%) and accuracy (&lt;20%), and stability. The limit of detection was 0.58 μg/L in urine and 1.47 μg/L in plasma for THPI and 1.14 and 2.17 μg/L, respectively, for PI. The described methods proved to be accurate and suitable to determine the toxicokinetics of both metabolites in human plasma and urine

Sharp optical phonon softening close to optimal doping in La2−x_{2-x}Bax_xCuO4+δ_{4+\delta}

We report a direct observation of a sharp Kohn-like anomaly in the doubly degenerate copper-oxygen bond-stretching phonon mode occurring at $\mathbf{q}\mathrm{=(0.3, 0,0)}$ in La$_{2-x}$Ba$_x$CuO$_{4+\delta}$ with $\mathrm{x=0.14\pm0.01}$, thanks to the high $\mathbf{Q}$ resolution of inelastic x-ray scattering. This anomaly is clearly seen when the inelastic signal is analysed using a single mode but is also consistent with a two mode hypothesis possibly due to a splitting of the degenerate modes due to symmetry breaking stripes. Our observation shows that the effect persists at the stripe propagation vector in a superconducting system close to optimal doping

Observation of low energy dispersive modes in un- derdoped (La, Nd) 2−x Sr x CuO 4

We find excitations lower in energy than known phonon modes in underdoped La$_{2-x}$Sr$_x$CuO$_{4+\delta}$ (x=0.08), with both inelastic X-Ray scattering (IXS) and inelastic neutron scattering (INS). A non dispersive excitation at 9 meV is identified and is also seen by INS in (La,Nd)$_{2-x}$Sr$_x$CuO$_{4+\delta}$, with 40$\%$ Nd substitution. INS also identifies a still lower energy dispersive mode at low q in the Nd free sample. These modes are clearly distinct from the longitudinal acoustic phonon and correspond in energy to the Zone Centre modes measured by optical spectroscopy and associated with stripe dynamics

Dynamic Distribution of Histone H4 Arginine 3 Methylation Marks in the Developing Murine Cortex

Epigenetic modifications regulate key transitions in cell fate during development of the central nervous system (CNS). During cortical development the initial population of proliferative neuroepithelial precursor cells give rise to neurons and then glia in a strict temporal order. Neurogenesis and gliogenesis are accompanied by a switch from symmetric to asymmetric divisions of the neural precursor cells generating another precursor and a differentiated progeny. To investigate whether specific post-translational histone modifications define specific stages of neural precursor differentiation during cortical development I focussed on the appearance of two different types of histone arginine methylation, the dimethyl symmetric H4R3 (H4R3me2s) and dimethyl asymmetric H4R3 (H4R3me2a) in the developing mouse cortex.An immunohistochemical study of the developing cortex at different developmental stages was performed to detect the distribution of H4R3me2s and H4R3me2a modifications. I analysed the distribution of these modifications in: 1) undifferentiated neural precursors, 2) post-mitotic neurons and 3) developing oligodendrocyte precursors (OLPs) using lineage-specific and histone modification-specific antibodies to co-label the cells. I found that the proliferative neuroepithelium during the stage of mainly symmetric expansive divisions is characterised by the prevalence of H4R3me2s modification and almost no detectable H4R3me2a modification. However, at a later stage, when the cortical layers with post-mitotic neurons have begun forming, both H4R3me2a and H4R3me2s modifications are detected in the post-mitotic neurons and in the developing OLPs.I propose that the H4R3me2s modification forms part of the "histone code" of undifferentiated neural precursors. The later appearance of the H4R3me2a modifications specifies the onset of neurogenesis and gliogenesis and the commitment of the NSCs to differentiate. Thus, the sequential appearance of the two different H4R3 methylation marks may define a particular cellular state of the NSCs during their development and differentiation demonstrating the role of histone arginine methylation in cortical development

Safety and immunogenicity of the candidate tuberculosis vaccine MVA85A in West Africa.

BACKGROUND: Vaccination with a recombinant modified vaccinia Ankara expressing antigen 85A from Mycobacterium tuberculosis, MVA85A, induces high levels of cellular immune responses in UK volunteers. We assessed the safety and immunogenicity of this new vaccine in West African volunteers. METHODS AND FINDINGS: We vaccinated 21 healthy adult male subjects (11 BCG scar negative and 10 BCG scar positive) with MVA85A after screening for evidence of prior exposure to mycobacteria. We monitored them over six months, observing for clinical, haematological and biochemical adverse events, together with assessment of the vaccine induced cellular immune response using ELISPOT and flow cytometry. MVA85A was well tolerated with no significant adverse events. Mild local and systemic adverse events were consistent with previous UK trials. Marked immunogenicity was found whether individuals had a previous BCG scar or not. There was not enhanced immunogenicity in those with a BCG scar, and induced T cell responses were better maintained in apparently BCG-naïve Gambians than previously studied BCG-naïve UK vaccinees. Although responses were predominantly attributable to CD4+ T cells, we also identified antigen specific CD8+ T cell responses, in subjects who were HLA B-35 and in whom enough blood was available for more detailed immunological analysis. CONCLUSIONS: These data on the safety and immunogenicity of MVA85A in West Africa support its accelerated development as a promising booster vaccine for tuberculosis. TRIAL REGISTRATION: ClinicalTrials.gov NCT00423839

G1 arrest and differentiation can occur independently of Rb family function

Repression of E2F target genes is required for cell cycle arrest in Rb family (Rb, p107, and p130)-deficient cells

The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

International audienceBACKGROUND:Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers.METHODS:Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort.RESULTS:For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, P trend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort P trend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98).CONCLUSIONS:These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers

Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores

Background: Recent population-based female breast cancer and prostate cancer polygenic risk scores (PRS) have been developed. We assessed the associations of these PRS with breast and prostate cancer risks for male BRCA1 and BRCA2 pathogenic variant carriers. Methods: 483 BRCA1 and 1318 BRCA2 European ancestry male carriers were available from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A 147-single nucleotide polymorphism (SNP) prostate cancer PRS (PRSPC) and a 313-SNP breast cancer PRS were evaluated. There were 3 versions of the breast cancer PRS, optimized to predict overall (PRSBC), estrogen receptor (ER)-negative (PRSER-), or ER-positive (PRSER+) breast cancer risk. Results: PRSER+ yielded the strongest association with breast cancer risk. The odds ratios (ORs) per PRSER+ standard deviation estimates were 1.40 (95% confidence interval [CI] =1.07 to 1.83) for BRCA1 and 1.33 (95% CI = 1.16 to 1.52) for BRCA2 carriers. PRSPC was associated with prostate cancer risk for BRCA1 (OR = 1.73, 95% CI = 1.28 to 2.33) and BRCA2 (OR = 1.60, 95% CI = 1.34 to 1.91) carriers. The estimated breast cancer odds ratios were larger after adjusting for female relative breast cancer family history. By age 85 years, for BRCA2 carriers, the breast cancer risk varied from 7.7% to 18.4% and prostate cancer risk from 34.1% to 87.6% between the 5th and 95th percentiles of the PRS distributions. Conclusions: Population-based prostate and female breast cancer PRS are associated with a wide range of absolute breast and prostate cancer risks for male BRCA1 and BRCA2 carriers. These findings warrant further investigation aimed at providing personalized cancer risks for male carriers and informing clinical management.Peer reviewe