Caloric restriction of db/db mice reverts hepatic steatosis and body weight with divergent hepatic metabolism

Non-alcoholic fatty liver disease (NAFLD) is one of the most frequent causes of liver disease and its prevalence is a serious and growing clinical problem. Caloric restriction (CR) is commonly recommended for improvement of obesity-related diseases such as NAFLD. However, the effects of CR on hepatic metabolism remain unknown. We investigated the effects of CR on metabolic dysfunction in the liver of obese diabetic db/db mice. We found that CR of db/db mice reverted insulin resistance, hepatic steatosis, body weight and adiposity to those of db/m mice. H-NMR- and UPLC-QTOF-MS-based metabolite profiling data showed significant metabolic alterations related to lipogenesis, ketogenesis, and inflammation in db/db mice. Moreover, western blot analysis showed that lipogenesis pathway enzymes in the liver of db/db mice were reduced by CR. In addition, CR reversed ketogenesis pathway enzymes and the enhanced autophagy, mitochondrial biogenesis, collagen deposition and endoplasmic reticulum stress in db/db mice. In particular, hepatic inflammation-related proteins including lipocalin-2 in db/db mice were attenuated by CR. Hepatic metabolomic studies yielded multiple pathological mechanisms of NAFLD. Also, these findings showed that CR has a therapeutic effect by attenuating the deleterious effects of obesity and diabetes-induced multiple complications

Orienting Attention Modulates Pain Perception: An ERP Study

2011-2012 > Academic research: refereed > Publication in refereed journalpublished_fina

Ultralight vector dark matter search using data from the KAGRA O3GK run

Among the various candidates for dark matter (DM), ultralight vector DM can be probed by laser interferometric gravitational wave detectors through the measurement of oscillating length changes in the arm cavities. In this context, KAGRA has a unique feature due to differing compositions of its mirrors, enhancing the signal of vector DM in the length change in the auxiliary channels. Here we present the result of a search for U(1)B−L gauge boson DM using the KAGRA data from auxiliary length channels during the first joint observation run together with GEO600. By applying our search pipeline, which takes into account the stochastic nature of ultralight DM, upper bounds on the coupling strength between the U(1)B−L gauge boson and ordinary matter are obtained for a range of DM masses. While our constraints are less stringent than those derived from previous experiments, this study demonstrates the applicability of our method to the lower-mass vector DM search, which is made difficult in this measurement by the short observation time compared to the auto-correlation time scale of DM

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects

Flavonoid Dimers as Bivalent Modulators for Pentamidine and Sodium Stiboglucanate Resistance in Leishmania

Drug resistance by overexpression of ATP-binding cassette (ABC) transporters is an impediment in the treatment of leishmaniasis. Flavonoids are known to reverse multidrug resistance (MDR) in Leishmania and mammalian cancers by inhibiting ABC transporters. Here, we found that synthetic flavonoid dimers with three (compound 9c) or four (compound 9d) ethylene glycol units exhibited a significantly higher reversing activity than other shorter or longer ethylene glycol-ligated dimers, with ∼3-fold sensitization of pentamidine and sodium stibogluconate (SSG) resistance in Leishmania, respectively. This modulatory effect was dosage dependent and not observed in apigenin monomers with the linker, suggesting that the modulatory effect is due to its bivalent nature. The mechanism of reversal activity was due to increased intracellular accumulation of pentamidine and total antimony in Leishmania. Compared to other MDR modulators such as verapamil, reserpine, quinine, quinacrine, and quinidine, compounds 9c and 9d were the only agents that can reverse SSG resistance. In terms of reversing pentamidine resistance, 9c and 9d have activities comparable to those of reserpine and quinacrine. Modulators 9c and 9d exhibited reversal activity on pentamidine resistance among LeMDR1(−/−), LeMDR1(+/+), and LeMDR1-overexpressed mutants, suggesting that these modulators are specific to a non-LeMDR1 pentamidine transporter. The LeMDR1 copy number is inversely related to pentamidine resistance, suggesting that it might be involved in importing pentamidine into the mitochondria. In summary, bivalency could be a useful strategy for the development of more potent ABC transporter modulators and flavonoid dimers represent a promising reversal agent for overcoming pentamidine and SSG resistance in parasite Leishmania

Investigation of a Magnetic Reconnection Event with Extraordinarily High Particle Energization in Magnetotail Turbulence

Magnetic reconnection and plasma turbulence are ubiquitous and key processes in the Universe. These two processes are suggested to be intrinsically related: magnetic reconnection can develop turbulence, and, in turn, turbulence can influence or excite magnetic reconnection. In this study, we report a rare and unique electron diffusion region (EDR) observed by the Magnetospheric Multiscale mission in the Earth’s magnetotail with significantly enhanced energetic particle fluxes. The EDR is in a region of strong turbulence within which the plasma density is dramatically depleted. We present three salient features. (1) Despite the turbulence, the EDR behaves nearly the same as that in 2D quasi-planar reconnection; the observations suggest that magnetic reconnection continues for several minutes. (2) The observed reconnection electric field and inferred energy transport are exceptionally large. However, the aspect ratio of the EDR (one definition of reconnection rate) is fairly typical. Instead, extraordinarily large-amplitude Hall electric fields appear to enable the strong energy transport. (3) We hypothesize that the high-energy transport rate, density depletion, and the strong particle acceleration are related to a near-runaway effect, which is due to the combination of low-plasma-density inflow (from lobes) and possible positive feedback between turbulence and reconnection. The detailed study on this EDR gives insight into the interplay between reconnection and turbulence, and the possible near-runaway effect, which may play an important role in other particle acceleration in astrophysical plasma

A Simple and Facile Approach to Aliphatic <i>N</i>‑Substituted Functional Eight-Membered Cyclic Carbonates and Their Organocatalytic Polymerization

Aliphatic <i>N</i>-substituted functional eight-membered cyclic carbonates were synthesized from <i>N</i>-substituted diethanolamines by intramolecular cyclization. On the basis of the <i>N</i>-substituent, three major subclasses of carbonate monomers were synthesized (<i>N</i>-aryl, <i>N</i>-alkyl and <i>N</i>-carbamate). Organocatalytic ring opening polymerization (ROP) of eight-membered cyclic carbonates was explored as a route to access narrowly dispersed polymers of predictable molecular weights. Polymerization kinetics was highly dependent on the substituent on the nitrogen atom and the catalyst used for the reaction. The use of triazabicyclodecene (TBD), instead of 1,8-diazabicyclo[5.4.0]­undec-7-ene (DBU), as the catalyst for the <i>N</i>-alkyl substituted monomers significantly enhanced the rate of polymerizations. Computational studies were performed to rationalize the observed trends for TBD catalyzed polymerizations. With the optimal organocatalyst all monomers could be polymerized generating well-defined polymers within a timespan of ≤2 h with relatively high monomer conversion (≥80%) and low molar-mass dispersity (<i><i>Đ</i></i>_M ≤ 1.3). Both the glass transition temperatures (<i>T</i>_g) and onset of degradation temperatures (<i>T</i>_onset) of these polymers were found to be <i>N</i>-substituent dependent and were in the range of about −45 to 35 °C and 230 to 333 °C, respectively. The copolymerization of the eight membered monomers with 6-membered cyclic comonomers including commercially available l-lactide and trimethylene carbonate produced novel copolymers. The combination of inexpensive starting materials, ease of ring-closure and subsequent polymerization makes this an attractive route to functional polycarbontes