Autophagy deficiency leads to protection from obesity and insulin resistance by inducing Fgf21 as a mitokine

Despite growing interest and a recent surge in papers, the role of autophagy in glucose and lipid metabolism is unclear. We produced mice with skeletal muscle–specific deletion of Atg7 (encoding autophagy-related 7). Unexpectedly, these mice showed decreased fat mass and were protected from diet-induced obesity and insulin resistance; this phenotype was accompanied by increased fatty acid oxidation and browning of white adipose tissue (WAT) owing to induction of fibroblast growth factor 21 (Fgf21). Mitochondrial dysfunction induced by autophagy deficiency increased Fgf21 expression through induction of Atf4, a master regulator of the integrated stress response. Mitochondrial respiratory chain inhibitors also induced Fgf21 in an Atf4-dependent manner. We also observed induction of Fgf21, resistance to diet-induced obesity and amelioration of insulin resistance in mice with autophagy deficiency in the liver, another insulin target tissue. These findings suggest that autophagy deficiency and subsequent mitochondrial dysfunction promote Fgf21 expression, a hormone we consequently term a 'mitokine', and together these processes promote protection from diet-induced obesity and insulin resistance

Evidence for a Self-Bound Liquid State and the Commensurate-Incommensurate Coexistence in 2D 3^3He on Graphite

We made heat-capacity measurements of two dimensional (2D) $^3$He adsorbed on graphite preplated with monolayer $^4$He in a wide temperature range (0.1 $\leq T \leq$ 80 mK) at densities higher than that for the 4/7 phase (= 6.8 nm$^{-2}$). In the density range of 6.8 $\leq \rho \leq$ 8.1 nm$^{-2}$, the 4/7 phase is stable against additional $^3$He atoms up to 20% and they are promoted into the third layer. We found evidence that such promoted atoms form a self-bound 2D Fermi liquid with an approximate density of 1 nm$^{-2}$ from the measured density dependence of the $\gamma$-coefficient of heat capacity. We also show evidence for the first-order transition between the commensurate 4/7 phase and the ferromagnetic incommensurate phase in the second layer in the density range of 8.1 $\leq \rho \leq$ 9.5 nm$^{-2}$.Comment: 6 pages, 4 figure

A single chemosensor for multiple analytes: fluorogenic and ratiometric absorbance detection of Zn²⁺, Mg²⁺ and F⁻, and its cell imaging

A simple coumarin based sensor 1 has been synthesized from the condensation reaction of 7-hydroxycoumarin and ethylenediamine via the intermediate 7-hydroxy-8-aldehyde-coumarin. As a multiple analysis sensor, 1 can monitor Zn²⁺ with the fluorescence enhanced at 457 nm, and ratiometric detection at 290 nm, 350 nm and 420 nm in DMF/H₂O (1/4, v/v) medium. Sensor 1 can also monitor Mg²⁺ with the fluorescence enhanced at 430 nm, and ratiometric detection at 290 nm, 370 nm and 430 nm in DMF medium through the interaction of chelation enhance fluorescence (CHEF) with metal ions. Furthermore, 1 also can monitor F⁻ with the fluorescence enhanced at 460 nm, and ratiometric detection at 290 nm and 390 nm in DMF medium simultaneously via hydrogen bonding and deprotonation with F− anion. Spectral titration, isothermal titration calorimetry and mass spectrometry revealed that the sensor formed a 1:1 complex with Mg²⁺, Zn²⁺ or F⁻, with stability constants of 4.5 × 10⁶, 3.4 × 10⁶, 8.0 × 10⁴ M⁻1 respectively. The complexation of the ions by 1 was an exothermic reaction driven by entropy processes. Furthermore, the sensor exhibits good membrane-permeability and was capable of monitoring at the intracellular Zn²⁺ level in living cells

Near infrared spectrometric investigation of lactate in a varying pH buffer

Lactic acidosis is commonly observed in various disease states in critical care and can be adopted as a hemodynamic biomarker, as well as a target for therapy. pH is the main biomarker for the diagnosis of acid–base disorders and is currently measured utilizing invasive blood sampling techniques. Therefore, there is a need for a non-invasive and continuous technology for the measurement of pH and lactate levels. In this work, near infrared spectroscopy is explored as a technique for investigating lactic acidosis. In-vitro studies on 20 isotonic phosphate buffer solutions of varying pH with constant lactate concentration (2 mmol/L) were performed. The whole near infrared spectrum (800–2600 nm) was then divided into four parts for analysis: (a) water absorption peaks, (b) 1000–1250 nm, (c) 1700–1760 nm, and (d) 2200–2400 nm. The water absorption peaks showed a linear variation with the changes in pH in the spectra. The range from 1700–1760 nm showed good correlation with calculated values for lactate ionization, with the changes in pH. However, the region from 2200–2400 nm showed a reverse correlation with respect to the concentration changes of lactate and a distinction could be made from pH 6–7 and 7–8. This study successfully identifies wavelengths (1233 nm, 1710 nm, 1750 nm, 2205 nm, 2319 nm, and 2341 nm) which can be directly correlated to lactic acidosis. Knowledge from this study will contribute toward the development of lactate-based pH monitoring optical sensor for critical care

Current-induced two-level fluctuations in pseudo spin-valves (Co/Cu/Co) nanostructures

Two-level fluctuations of the magnetization state of pseudo spin-valve pillars Co(10 nm)/Cu(10 nm)/Co(30 nm) embedded in electrodeposited nanowires (~40 nm in diameter, 6000 nm in length) are triggered by spin-polarized currents of 10^7 A/cm^2 at room temperature. The statistical properties of the residence times in the parallel and antiparallel magnetization states reveal two effects with qualitatively different dependences on current intensity. The current appears to have the effect of a field determined as the bias field required to equalize these times. The bias field changes sign when the current polarity is reversed. At this field, the effect of a current density of 10^7 A/cm^2 is to lower the mean time for switching down to the microsecond range. This effect is independent of the sign of the current and is interpreted in terms of an effective temperature for the magnetization.Comment: 4 pages, 5 figures, revised version, to be published in Phys. Rev. Let

Optogalvanic Spectroscopy of Metastable States in Yb^{+}

The metastable ^{2}F_{7/2} and ^{2}D_{3/2} states of Yb^{+} are of interest for applications in metrology and quantum information and also act as dark states in laser cooling. These metastable states are commonly repumped to the ground state via the 638.6 nm ^{2}F_{7/2} -- ^{1}D[5/2]_{5/2} and 935.2 nm ^{2}D_{3/2} -- ^{3}D[3/2]_{1/2} transitions. We have performed optogalvanic spectroscopy of these transitions in Yb^{+} ions generated in a discharge. We measure the pressure broadening coefficient for the 638.6 nm transition to be 70 \pm 10 MHz mbar^{-1}. We place an upper bound of 375 MHz/nucleon on the 638.6 nm isotope splitting and show that our observations are consistent with theory for the hyperfine splitting. Our measurements of the 935.2 nm transition extend those made by Sugiyama et al, showing well-resolved isotope and hyperfine splitting. We obtain high signal to noise, sufficient for laser stabilisation applications.Comment: 8 pages, 5 figure

Linear Dichroism and Orientation of the Phycomyces Photopigment

The greater sensitivity of a cylindrical Phycomyces sporangiophore to blue light polarized transversely rather than longitudinally is a consequence of the dichroism and orientation of the receptor pigment. The abilities of wild type and several carotene mutants to distinguish between the two directions of polarization are the same. The E-vector angle for maximum response relative to the transverse direction is 42 ± 4° at 280 nm, 7° ± 3° at 456 nm, and 7° ± 8° at 486 nm. The in vivo attenuation of polarized light at these wavelengths is very small. The polarized light effect in Phycomyces cannot arise from reflections at the cell surface or from differential attenuations due to internal screening or scattering