Stat3 promotes mitochondrial transcription and oxidative respiration during maintenance and induction of naive pluripotency.

Transcription factor Stat3 directs self-renewal of pluripotent mouse embryonic stem (ES) cells downstream of the cytokine leukemia inhibitory factor (LIF). Stat3 upregulates pivotal transcription factors in the ES cell gene regulatory network to sustain naïve identity. Stat3 also contributes to the rapid proliferation of ES cells. Here, we show that Stat3 increases the expression of mitochondrial-encoded transcripts and enhances oxidative metabolism. Chromatin immunoprecipitation reveals that Stat3 binds to the mitochondrial genome, consistent with direct transcriptional regulation. An engineered form of Stat3 that localizes predominantly to mitochondria is sufficient to support enhanced proliferation of ES cells, but not to maintain their undifferentiated phenotype. Furthermore, during reprogramming from primed to naïve states of pluripotency, Stat3 similarly upregulates mitochondrial transcripts and facilitates metabolic resetting. These findings suggest that the potent stimulation of naïve pluripotency by LIF/Stat3 is attributable to parallel and synergistic induction of both mitochondrial respiration and nuclear transcription factors.GM’s laboratory is supported by grants from Armenise-Harvard Foundation and Telethon Foundation (TCP13013). The Cambridge Stem Cell Institute receives core funding from the Wellcome Trust and Medical Research Council. GM was supported by a Human Frontier Science Program Fellowship. AS is a Medical Research Professor.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.15252/embj.20159262

Site-selective Probe of Magnetic Excitations in Rare-earth Nickelates using Resonant Inelastic X-ray Scattering

We have used high-resolution resonant inelastic x-ray scattering (RIXS) to study a thin film of NdNiO$_3$, a compound whose unusual spin- and bond-ordered electronic ground state has been of long-standing interest. Below the magnetic ordering temperature, we observe well-defined collective magnon excitations along different high-symmetry directions in momentum space. The magnetic spectra depend strongly on the incident photon energy, which we attribute to RIXS coupling to different local electronic configurations of the expanded and compressed NiO$_6$ octahedra in the bond-ordered state. Both the noncollinear magnetic ground state and the observed site-dependent magnon excitations are well described by a model that assumes strong competition between the antiferromagnetic superexchange and ferromagnetic double-exchange interactions. Our study provides direct insight into the magnetic dynamics and exchange interactions of the rare-earth nickelates, and demonstrates that RIXS can serve as a site-selective probe of magnetism in these and other materials.Comment: Phys. Rev. X, in pres

Dynamical charge density fluctuations pervading the phase diagram of a Cu-based high-Tc superconductor

Charge density waves are a common occurrence in all families of high critical temperature superconducting cuprates. Although consistently observed in the underdoped region of the phase diagram and at relatively low temperatures, it is still unclear to what extent they influence the unusual properties of these systems. Using resonant x-ray scattering we carefully determined the temperature dependence of charge density modulations in (Y,Nd)Ba$_2$Cu$_3$O$_{7-{\delta}}$ for three doping levels. We discovered short-range dynamical charge density fluctuations besides the previously known quasi-critical charge density waves. They persist up to well above the pseudogap temperature T*, are characterized by energies of few meV and pervade a large area of the phase diagram, so that they can play a key role in shaping the peculiar normal-state properties of cuprates.Comment: 34 pages, 4 figures, 11 supplementary figure

Polarization resolved Cu L3L_3-edge resonant inelastic x-ray scattering of orbital and spin excitations in NdBa2_{2}Cu3_{3}O7−δ_{7-\delta}

High resolution resonant inelastic x-ray scattering (RIXS) has proven particularly effective in the determination of crystal field and spin excitations in cuprates. Its strength lies in the large Cu $L_{3}$ resonance and in the fact that the scattering cross section follows quite closely the single-ion model predictions, both in the insulating parent compounds and in the superconducting doped materials. However, the spectra become increasingly broader with (hole) doping, hence resolving and assigning spectral features has proven challenging even with the highest energy resolution experimentally achievable. Here we have overcome this limitation by measuring the complete polarization dependence of the RIXS spectra as function of momentum transfer and doping in thin films of NdBa$_{2}$Cu$_{3}$O$_{7-\delta}$. Besides confirming the previous assignment of $dd$ and spin excitations (magnon, bimagnon) in the antiferromagnetic insulating parent compound, we unequivocally single out the actual spin-flip contribution at all dopings. We also demonstrate that the softening of $dd$ excitations is mainly attributed to the shift of the $xy$ peak to lower energy loss. These results provide a definitive assessment of the RIXS spectra of cuprates and demonstrate that RIXS measurements with full polarization control are practically feasible and highly informative.Comment: 14 pages, 10 figure

C7 is expressed on endothelial cells as a trap for the assembling terminal complement complex and may exert anti-inflammatory function

We describe a novel localization of C7 as a membrane-bound molecule on endothelial cells (ECs). Data obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), Western blot analysis, Northern blot analysis, and mass spectrometry revealed that membrane- associated C7 (mC7) was indistinguish-able from soluble C7 and was associated with vimentin on the cell surface. mC7 interacted with the other late complement components to form membrane-bound TCC (mTCC). Unlike the soluble SC5b-9, mTCC failed to stimulate ECs to express adhesion molecules, to secrete IL-8, and to induce albumin leakage through a monolayer of ECs, and more importantly protected ECs from the proinflammatory effect of SC5b-9. Our data disclose the possibility of a novel role of mC7 that acts as a trap for the late complement components to control excessive inflammation induced by SC5b-9. \ua9 2009 by The American Society of Hematology

Mini-invasive approach to preneoplastic and neoplastic endometrial lesions. Comparative study among histological, cytological and immunohistochemical diagnosis

Objective: To compare the accuracy of cytology plus immunoistochemistry vs histology in the preoperative diagnosis of endometrial malignancy. Methods: We prospectively analyzed 142 women with a proliferative endometrial lesion undergoing operative hysteroscopy (ISC): at the time of ISC, the fluid used for saline contrast sonohysterography (SCSH) was collected for cytological analysis and compared to histology. In 9 women a markers board (Notch-1+ER-\u3b1+PR-\u3b2) expression was analyzed semiquantitatively in term of presence and intensity, on both glandular and stromal samples. Results: Table 1 shows the comparison between cytological and histological diagnosis. ISC histological results Benign Lesions n=134 Malignant Lesions n=8 Endometrial Polyps n=124 Hypertrophy n=3 Typical hyperplasia n=7 Atypical hyperplasia n=4 Cancer n=4 CTM - 0 0 0 0 0 CTM + 0 0 0 0 3 SCSH cytological results Atypia - 116 3 6 1 0 Atypia + 2 0 0 3 3 Inadequate (5%) 5 (4 cervical cells) (1 scant sample) 0 1 (1 cervical cells) 0 1 (hypocellulated) Cytological sampling was inadequate in 7 cases (5%). The K value between cytology and histology was 98.4% for benign and 85.7% for malignant lesions. Notch-1 revealed a changing expression pattern: absent in benign lesions, focal and marked in atypical hyperplasia and widespread and marked in cancers. Moreover Notch-1 expression was mild and focal in originally cyto-hystologycal benign lesions which turned into atypical hyperplasia during follow up. In cancer cases, ER-\u3b1 and PR-\u3b2 were widespread and markedly expressed either in the glandular or stromal layer. Conclusions: Cytological analysis could be used as a screening test, at least for women at high surgical risk. Notch-1+ER-\u3b1+PR-\u3b2 expression could be predictive for the risk of endometrial malignancy even at an earlier stadium than hyperplasia and could be used to identify the glandular or stromal origin of cancer thus helping in identifying women at increased risk of malignancy

Symmetry breaking at the (111) interfaces of SrTiO3{_3} hosting a 2D-electron system

We used x-ray absorption spectroscopy to study the orbital symmetry and the energy band splitting of (111) LaAlO${_3}$/SrTiO${_3}$ and LaAlO${_3}$/EuTiO${_3}$/SrTiO${_3}$ heterostructures, hosting a quasi two-dimensional electron system (q2DES), and of a Ti-terminated (111) SrTiO${_3}$ single crystal, also known to form a q2DES at its surface. We demonstrate that the bulk tetragonal Ti-3d D${_4}$${_h}$ crystal field is turned into trigonal D${_3}$${_d}$ crystal field in all cases. The symmetry adapted a${_1}$${_g}$ and e${^\pi_g}$ orbitals are non-degenerate in energy and their splitting, \Delta, is positive at the bare STO surface but negative in the heterostructures, where the a${_1}$${_g}$ orbital is lowest in energy. These results demonstrate that the interfacial symmetry breaking induced by epitaxial engineering of oxide interfaces has a dramatic effect on their electronic properties, and it can be used to manipulate the ground state of the q2DES.Comment: 6 pages article, plus 5 pages supplementary informatio