The APC/C Coordinates Retinal Differentiation with G1 Arrest through the Nek2-Dependent Modulation of Wingless Signaling

The cell cycle is coordinated with differentiation during animal development. Here we report a cell-cycle-independent developmental role for a master cell-cycle regulator, the anaphase-promoting complex or cyclosome (APC/C), in the regulation of cell fate through modulation of Wingless (Wg) signaling. The APC/C controls both cell-cycle progression and postmitotic processes through ubiquitin-dependent proteolysis. Through an RNAi screen in the developing $\textit{Drosophila}$eye, we found that partial APC/C inactivation severely inhibits retinal differentiation independently of cell-cycle defects. The differentiation inhibition coincides with hyperactivation of Wg signaling caused by the accumulation of a Wg modulator, $\textit{Drosophila}$ Nek2 (dNek2). The APC/C degrades dNek2 upon synchronous G1 arrest prior to differentiation, which allows retinal differentiation through local suppression of Wg signaling. We also provide evidence that decapentaplegic signaling may posttranslationally regulate this APC/C function. Thus, the APC/C coordinates cell-fate determination with the cell cycle through the modulation of developmental signaling pathways.T.M. and F.M. were partly supported by a CRUK Fellowship to Y.K. T.M. thanks the European Commission for a Marie Curie fellowship

Quasi-Two-Dimensional Fermi Surfaces and Coherent Interlayer Transport in KFe2_2As2_2

We report the results of the angular-dependent magnetoresistance oscillations (AMROs), which can determine the shape of bulk Fermi surfaces in quasi-two-dimensional (Q2D) systems, in a highly hole-doped Fe-based superconductor KFe$_2$As$_2$ with $T_c \approx$ 3.7 K. From the AMROs, we determined the two Q2D FSs with rounded-square cross sections, corresponding to 12% and 17% of the first Brillouin zone. The rounded-squared shape of the FS cross section is also confirmed by the analyses of the interlayer transport under in-plane fields. From the obtained FS shape, we infer the character of the 3d orbitals that contribute to the FSs.Comment: 4 pages, 4 figures, accepted in Phys. Rev. Let

PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK- and IRE1α-mediated unfolded protein response

Poly(ADP-ribose) polymerases (PARPs; also known as ADP-ribosyl transferase D proteins) modify acceptor proteins with ADP-ribose modifications of varying length (reviewed in refs 1, 2, 3). PARPs regulate key stress response pathways, including DNA damage repair and the cytoplasmic stress response. Here, we show that PARPs also regulate the unfolded protein response (UPR) of the endoplasmic reticulum (ER). Human PARP16 (also known as ARTD15) is a tail-anchored ER transmembrane protein required for activation of the functionally related ER stress sensors PERK and IRE1α during the UPR. The third identified ER stress sensor, ATF6, is not regulated by PARP16. As is the case for other PARPs that function during stress, the enzymatic activity of PARP16 is upregulated during ER stress when it ADP-ribosylates itself, PERK and IRE1α. ADP-ribosylation by PARP16 is sufficient for activating PERK and IRE1α in the absence of ER stress, and is required for PERK and IRE1α activation during the UPR. Modification of PERK and IRE1α by PARP16 increases their kinase activities and the endonuclease activity of IRE1α. Interestingly, the carboxy-terminal luminal tail of PARP16 is required for PARP16 function during ER stress, suggesting that it transduces stress signals to the cytoplasmic PARP catalytic domain.National Cancer Institute (U.S.) (Cancer Center Support Core Grant P30-CA14051)National Institutes of Health (U.S.) (Grant 5R01 GM087465-02)Kathy and Curt Marble Cancer Research FundJeptha H. and Emily V. Wade FundVirginia and D.K. Ludwig Fund for Cancer Researc

Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV) following in vivo escape from neutralising antibody

<b>BACKGROUND:</b> In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.<p></p> <b>RESULTS:</b> Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.<p></p> <b>CONCLUSIONS:</b> The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.<p></p&gt

Anomalous vortex dynamics in spin-triplet superconductor UTe2_2

The vortex dynamics in the spin-triplet superconductor, UTe$_2$, are studied by measuring the DC electrical resistivity with currents along the $a$-axis under magnetic fields along the $b$-axis. Surprisingly, we have discovered an island region of low critical current deep inside the superconducting (SC) state, well below the SC upper critical field, attributed to a weakening of vortex pinning. Notably, this region coincides with the recently proposed intermediate-field SC state. We discuss the possibility of nonsingular vortices in the intermediate state, where SC order parameter does not vanish entirely in the vortex cores due to the mixing of multiple SC components

Detection of the interfacial exchange field at a ferromagnetic insulator-nonmagnetic metal interface with pure spin currents

At the interface between a nonmagnetic metal (NM) and a ferromagnetic insulator (FI) spin current can interact with the magnetization, leading to a modulation of the spin current. The interfacial exchange field at these FI-NM interfaces can be probed by placing the interface in contact with the spin transport channel of a lateral spin valve (LSV) device and observing additional spin relaxation processes. We study interfacial exchange field in lateral spin valve devices where Cu spin transport channel is in proximity with ferromagnetic insulator EuS (EuS-LSV) and yttrium iron garnet Y$_3$Fe$_5$O$_{12}$ (YIG-LSV). The spin signals were compared with reference lateral spin valve devices fabricated on nonmagnetic Si/SiO$_2$ substrate with MgO or AlO$_x$ capping. The nonlocal spin valve signal is about 4 and 6 times lower in the EuS-LSV and YIG-LSV, respectively. The suppression in the spin signal has been attributed to enhanced surface spin-flip probability at the Cu-EuS (or Cu-YIG) interface due to interfacial spin-orbit field. Besides spin signal suppression we also found widely observed low temperature peak in the spin signal at $T \sim$30 K is shifted to higher temperature in the case of devices in contact with EuS or YIG. Temperature dependence of spin signal for different injector-detector distances reveal fluctuating exchange field at these interfaces cause additional spin decoherence which limit spin relaxation time in addition to conventional sources of spin relaxation. Our results show that temperature dependent measurement with pure spin current can be used to probe interfacial exchange field at the ferromagnetic insulator-nonmagnetic metal interface.Comment: 10 pages, 3 figures, accepted in Physical Review

Reinforcement of superconductivity by quantum critical fluctuations of metamagnetism in UTe2_2

The normal-conducting state of the superconductor UTe$_2$ is studied by entropy analysis for magnetic fields along the $b$-axis, obtained from magnetization using the relation $(\partial M/\partial T)_B=(\partial S/\partial B)_T$. We observe a strong increase in entropy with magnetic field due to metamagnetic fluctuations (spatially uniform, $Q=0$). The field dependence is well described by the Hertz-Millis-Moriya theory for quantum criticality of itinerant metamagnetism. Notably, the lower bound of the quantum-critical region coincides well with the position of the minimum in the superconducting transition temperature $T_c(B)$. Hence, our results suggest that $Q=0$ fluctuations reinforce the superconductivity.Comment: accepted as a Letter in Phys. Rev.

Quantum oscillations in a centrosymmetric skyrmion-hosting magnet GdRu2Si2

We have performed magnetic torque and resistivity measurements on a centrosymmetric skyrmion-host GdRu2Si2, in which the dominant magnetic interaction leading to skyrmion formation is under debate. We observe both the de Haas-van Alphen and Shubnikov-de Haas oscillations in the forced ferromagnetic phase. The angular dependence of the quantum oscillation frequencies can be reproduced by the ab-initio calculation. The de Haas-van Alphen oscillation is also observed in the double-Q phase with a different frequency to that in the forced ferromagnetic phase, indicating a Fermi surface reconstruction due to the coupling between localized spins and conduction electrons. Based on these experimental findings, the magnetic interactions in this system are discussed.Comment: 11 pages, 8 figure