Mechanistic target of rapamycin (mTOR) implicated in plasticity of the reproductive axis during social status transitions

© 2019 Elsevier Inc. The highly conserved brain-pituitary-gonadal (BPG) axis controls reproduction in all vertebrates, so analyzing the regulation of this signaling cascade is important for understanding reproductive competence. The protein kinase mechanistic target of rapamycin (mTOR) functions as a conserved regulator of cellular growth and metabolism in all eukaryotes, and also regulates the reproductive axis in mammals. However, whether mTOR might also regulate the BPG axis in non-mammalian vertebrates remains unexplored. We used complementary experimental approaches in an African cichlid fish, Astatotilapia burtoni, to demonstrate that mTOR is involved in regulation of the brain, pituitary, and testes when males rise in rank to social dominance. mTOR or downstream components of its signaling pathway (p-p70S6K) were detected in gonadotropin-releasing hormone (GnRH1) neurons, the pituitary, and testes. Transcript levels of mtor in the pituitary and testes also varied when reproductively-suppressed subordinate males rose in social rank to become dominant reproductively-active males, a transition similar to puberty in mammals. Intracerebroventricular injection of the mTORC1 inhibitor, rapamycin, revealed a role for mTOR in the socially-induced hypertrophy of GnRH1 neurons. Rapamycin treatment also had effects at the pituitary and testes, suggesting involvement of the mTORC1 complex at multiple levels of the reproductive axis. Thus, we show that mTOR regulation of BPG function is conserved to fishes, likely playing important roles in regulating reproduction and fertility across all male vertebrates

Configuration for Micro pH Sensor

A fully integrated pH sensor with a built-in reference electrode is proposed. An iridium oxide microelectrode and a pH-insensitive field-effect transistor are used as a pH sensor and a reference electrode, respectively. The sensitivity of the proposed device matches well with the estimated value to within 0.3 mV/pH deviation

Emergence of robust 2D skyrmions in SrRuO3 ultrathin film without the capping layer

Magnetic skyrmions have fast evolved from a novelty, as a realization of topologically protected structure with particle-like character, into a promising platform for new types of magnetic storage. Significant engineering progress was achieved with the synthesis of compounds hosting room-temperature skyrmions in magnetic heterostructures, with the interfacial Dzyaloshinskii-Moriya interactions (DMI) conducive to the skyrmion formation. Here we report findings of ultrathin skyrmion formation in a few layers of SrRuO3 grown on SrTiO3 substrate without the heavy-metal capping layer. Measurement of the topological Hall effect (THE) reveals a robust stability of skyrmions in this platform, judging from the high value of the critical field 1.57 Tesla (T) at low temperature. THE survives as the field is tilted by as much as 85 degrees at 10 Kelvin, with the in-plane magnetic field reaching up to 6.5 T. Coherent Bragg Rod Analysis, or COBRA for short, on the same film proves the rumpling of the Ru-O plane to be the source of inversion symmetry breaking and DMI. First-principles calculations based on the structure obtained from COBRA find significant magnetic anisotropy in the SrRuO3 film to be the main source of skyrmion robustness. These features promise a few-layer SRO to be an important new platform for skyrmionics, without the necessity of introducing the capping layer to boost the spin-orbit coupling strength artificially.Comment: Supplementary Information available upon reques

Emergence of robust 2D skyrmions in SrRuO3 ultrathin film without the capping layer

Magnetic skyrmions have fast evolved from a novelty, as a realization of topologically protected structure with particle-like character, into a promising platform for new types of magnetic storage. Significant engineering progress was achieved with the synthesis of compounds hosting room-temperature skyrmions in magnetic heterostructures, with the interfacial Dzyaloshinskii-Moriya interactions (DMI) conducive to the skyrmion formation. Here we report findings of ultrathin skyrmion formation in a few layers of SrRuO3 grown on SrTiO3 substrate without the heavy-metal capping layer. Measurement of the topological Hall effect (THE) reveals a robust stability of skyrmions in this platform, judging from the high value of the critical field 1.57 Tesla (T) at low temperature. THE survives as the field is tilted by as much as 85 degrees at 10 Kelvin, with the in-plane magnetic field reaching up to 6.5 T. Coherent Bragg Rod Analysis, or COBRA for short, on the same film proves the rumpling of the Ru-O plane to be the source of inversion symmetry breaking and DMI. First-principles calculations based on the structure obtained from COBRA find significant magnetic anisotropy in the SrRuO3 film to be the main source of skyrmion robustness. These features promise a few-layer SRO to be an important new platform for skyrmionics, without the necessity of introducing the capping layer to boost the spin-orbit coupling strength artificially.Comment: Supplementary Information available upon reques

Mechanisms and energetics of free radical initiated disulfide bond cleavage in model peptides and insulin by mass spectrometry

We investigate the mechanism of disulfide bond cleavage in gaseous peptide and protein ions initiated by a covalently-attached regiospecific acetyl radical using mass spectrometry (MS). Highly selective S–S bond cleavages with some minor C–S bond cleavages are observed by a single step of collisional activation. We show that even multiple disulfide bonds in intact bovine insulin are fragmented in the MS2 stage, releasing the A- and B-chains with a high yield, which has been challenging to achieve by other ion activation methods. Yet, regardless of the previous reaction mechanism studies, it has remained unclear why (1) disulfide bond cleavage is preferred to peptide backbone fragmentation, and why (2) the S–S bond that requires the higher activation energy conjectured in previously suggested mechanisms is more prone to be cleaved than the C–S bond by hydrogen-deficient radicals. To probe the mechanism of these processes, model peptides possessing deuterated β-carbon(s) at the disulfide bond are employed. It is suggested that the favored pathway of S–S bond cleavage is triggered by direct acetyl radical attack at sulfur with concomitant cleavage of the S–S bond (S_H2). The activation energy for this process is substantially lower by ~9–10 kcal mol^(−1) than those of peptide backbone cleavage processes determined by density functional quantum chemical calculations. Minor reaction pathways are initiated by hydrogen abstraction from the α-carbon or the β-carbon of a disulfide, followed by β-cleavages yielding C–S or S–S bond scissions. The current mechanistic findings should be generally applicable to other radical-driven disulfide bond cleavages with different radical species such as the benzyl and methyl pyridyl radicals

A Case of Autoimmune Pancreatitis Manifested by a Pseudocyst and IgG4-Associated Cholangitis

Autoimmune pancreatitis (AIP) is a benign disorder and a unique form of chronic pancreatitis with several characteristic features. A cystic formation that mimics a pseudocyst is a rare finding. There have been a few reports of AIP complicated by pancreatic cysts. We present a case of AIP with multiple pseudocysts and obstructive jaundice caused by IgG4-associated cholangitis. We initially missed the diagnosis due to the pseudocyst. Based on the computed tomography images, laboratory findings and the therapeutic response to steroids, the case was diagnosed as AIP with pseudocysts and associated cholangiopathy

The Globular Cluster System of M60 (NGC 4649). I. CFHT MOS Spectroscopy and Database

We present the measurement of radial velocities for globular clusters in M60, giant elliptical galaxy in the Virgo cluster. Target globular cluster candidates were selected using the Washington photometry based on the deep 16\arcmin \times 16\arcmin images taken at the KPNO 4m and using the $VI$ photometry derived from the HST/WFPC2 archive images. The spectra of the target objects were obtained using the Multi-Object Spectrograph (MOS) at the Canada-France-Hawaii Telescope (CFHT). We have measured the radial velocity for 111 objects in the field of M60: 93 globular clusters (72 blue globular clusters with $1.0\le(C-T_1)<1.7$ and 21 red globular clusters with $1.7\le(C-T_1)<2.4$), 11 foreground stars, 6 small galaxies, and the nucleus of M60. The measured velocities of the 93 globular clusters range from $\sim 500$ km s$^{-1}$ to $\sim 1600$ km s$^{-1}$, with a mean value of $1070_{-25}^{+27}$ km s$^{-1}$, which is in good agreement with the velocity of the nucleus of M60 ($v_{\rm gal}=1056$ km s$^{-1}$). Combining our results with data in the literature, we present a master catalog of radial velocities for 121 globular clusters in M60. The velocity dispersion of the globular clusters in the master catalog is found to be $234_{-14}^{+13}$ km s$^{-1}$ for the entire sample, $223_{-16}^{+13}$ km s$^{-1}$ for 83 blue globular clusters, and $258_{-31}^{+21}$ km s$^{-1}$ for 38 red globular clusters.Comment: 29 pages, 8 figures. To appear in Ap

The Globular Cluster System of M60 (NGC 4649). II. Kinematics of the Globular Cluster System

We present a kinematic analysis of the globular cluster (GC) system in the giant elliptical galaxy (gE) M60 in the Virgo cluster. Using the photometric and spectroscopic database of 121 GCs (83 blue GCs and 38 red GCs), we have investigated the kinematics of the GC system. We have found that the M60 GC system shows a significant overall rotation. The rotation amplitude of the blue GCs is slightly smaller than or similar to that of the red GCs, and their angles of rotation axes are similar. The velocity dispersions about the mean velocity and about the best fit rotation curve for the red GCs are marginally larger than those for the blue GCs. Comparison of observed stellar and GC velocity dispersion profiles with those calculated from the stellar mass profile shows that the mass-to-light ratio should be increased as the galactocentric distance increases, indicating the existence of an extended dark matter halo. The entire sample of GCs in M60 is found to have a tangentially biased velocity ellipsoid unlike the GC systems in other gEs. Two subsamples appear to have different velocity ellipsoids. The blue GC system has a modest tangentially biased velocity ellipsoid, while the red GC system has a modest radially biased or an isotropic velocity ellipsoid. From the comparison of the kinematic properties of the M60 GC system to those of other gEs (M87, M49, NGC 1399, NGC 5128, and NGC 4636), it is found that the velocity dispersion of the blue GC system is similar to or larger than that of the red GC system except for M60, and the rotation of the GC system is not negligible. The entire sample of each GC system shows an isotropic velocity ellipsoid except for M60, while the subsamples show diverse velocity ellipsoids. We discuss the implication of these results for the formation models of the GC system in gEs.Comment: 48 pages, 16 figures. To appear in Ap