Liver regeneration requires spatially and temporally precisely coordinated proliferation of the two major hepatic cell populations, hepatocytes and liver sinusoidal endothelial cells (LSECs), to reconstitute liver structure and function. The underlying mechanisms of this complex molecular cross-talk remain elusive. Here, we show that the expression of Angiopoietin-2 (Ang2) in LSECs is dynamically regulated after partial hepatectomy. During the early inductive phase of liver regeneration, Ang2 down-regulation leads to reduced LSEC transforming growth factor-β1 production, enabling hepatocyte proliferation by releasing an angiocrine proliferative brake. During the later angiogenic phase of liver regeneration, recovery of endothelial Ang2 expression enables regenerative angiogenesis by controlling LSEC vascular endothelial growth factor receptor 2 expression. The data establish LSECs as a dynamic rheostat of liver regeneration, spatiotemporally orchestrating hepatocyte and LSEC proliferation through angiocrine- and autocrine-acting Ang2, respectively.

IntroductionFOXO1 belongs to the subgroup O of forkhead transcription factors (FOX), which share the highly conserved forkhead DNAbinding domain. This O subgroup consists of the 4 members, FOXO1, FOXO3, FOXO4, and FOXO6. 1 FOXO transcription factors control different cellular processes, such as stress response, proliferation, apoptosis, and cell differentiation. 2 FOXO target genes include the cell-cycle regulators CDKN1A and CDKN1B, proapoptotic genes BIM, PMAIP1/NOXA, and FASL as well as oxidative stress protectors SOD2 and CAT. 1,3,4 FOXO1 is of particular interest in B cells because it is highly expressed (http://biogps.gnf.org) and plays a nonredundant role in B-cell differentiation by activating recombination activating genes Rag1 and Rag2 and germinal center (GC) genes Bcl6 and Aicda. [5][6][7] In addition, FOXO1 was reported to be a regulator of B-cell death, and its inactivation by B-cell receptor signaling to AKT/PKB kinase was found to be critical for survival of mature B cells. 8 Several other kinases, including the IB kinase 9 and ERK, 10 have been identified to phosphorylate and facilitate nuclear export of FOXO proteins.It is well documented that the oncogenic program of B-cell lymphomas (BCLs) is tightly related to the survival program of their nontransformed precursor cells. In the majority of nonHodgkin BCLs, the oncogenic program is established as an error of normal GC processes (ie, somatic hypermutation and class switch recombination), which facilitate mutations of tumor suppressor genes and translocation of oncogenes. 11 Execution of the oncogenic program in these lymphomas requires the maintenance of the GC program and the prevention of post-GC differentiation steps (eg, by BCL6 and PAX5 translocation) 12 and probably by deregulation of other transcription factors regulating GC phenotype and terminal differentiation of B cells. 13 Unlike other types of BCLs, neoplastic cells of classical Hodgkin lymphoma (cHL) lose most of their B-cell phenotype. 14 At the same time, Hodgkin and Reed-Sternberg (HRS) cells express many genes of activated B cells, indicating that the oncogenic program of cHL may arise in the process of deregulation of mechanisms, controlling activity of NF-B, 15 ERK, 16 and JAK/STAT 17 pathways in activated B cells. In addition, AKT and ERK kinases are frequently constitutively activated in different B-lymphoma entities, including follicular lymphoma (FL), 18 diffuse large BCL (DLBCL), 19 Burkitt lymphoma (BL), 20 and cHL. 21,22 Therefore, it has been hypothesized that FOXO1 inactivation might be a common event contributing to lymphomagenesis in several lymphoma entities. 8 Given the proposed critical role of inactivation of FOXO1 function in BCLs, we investigated FOXO1 expression in different BCL entities. Unexpectedly, whereas FOXO1 expression was maintained in majority of non-Hodgkin lymphomas (NHLs), downregulation was observed in cHL and lymphocyte-predominant Hodgkin lymphoma (LPHL). We found that re-expression of FOXO1 inhibited proliferation and induced apoptosis in ...

Transverse magnetothermoelectric effects are studied in Permalloy thin films grown on MgO and GaAs substrates and compared to those grown on suspended SiN(x) membranes. The transverse voltage along platinum strips patterned on top of the Permalloy films is measured versus the external magnetic field as a function of the angle and temperature gradients. After the identification of the contribution of the planar and anomalous Nernst effects, we find an upper limit for the transverse spin Seebeck effect, which is several orders of magnitude smaller than previously reported.

Electrons in organic semiconductors (OSC) possess remarkably long spin relaxation times. Hybrid spintronic devices that combine OSC with ferromagnetic (FM) substrates are therefore expected to provide a route to devices with improved and new functionalities. A crucial role is played by the FM‐OSC interface which governs the spin injection into the OSC. Using spin‐resolved photoelectron spectroscopy and ab initio calculations we study here such possible injection channels in metal phthalocyanines (MPc). We report the first direct observation of the successful engineering of different spin‐selective hybrid interface states at the Fermi level of a FM‐OSC hybrid junction only by changing the central metal atom of a MPc. Our results demonstrate that tailoring the chemical interaction at the FM‐OSC interface is a promising way to modify the spin injection channels and thus the spin injection capability.