In utero exposure to Δ9‐tetrahydrocannabinol leads to postnatal catch‐up growth and dysmetabolism in the adult rat liver

The rates of gestational cannabis use have increased despite limited evidence for its safety in fetal life. Recent animal studies demonstrate that prenatal exposure to Δ9‐tetrahydrocannabinol (Δ9‐THC, the psychoactive component of cannabis) promotes intrauterine growth restriction (IUGR), culminating in postnatal metabolic deficits. Given IUGR is associated with impaired hepatic function, we hypothesized that Δ9‐THC offspring would exhibit hepatic dyslipidemia. Pregnant Wistar rat dams received daily injections of vehicular control or 3 mg/kg Δ9‐THC i.p. from embry-onic day (E) 6.5 through E22. Exposure to Δ9‐THC decreased the liver to body weight ratio at birth, followed by catch‐up growth by three weeks of age. At six months, Δ9‐THC‐exposed male offspring exhibited increased visceral adiposity and higher hepatic triglycerides. This was instigated by augmented expression of enzymes involved in triglyceride synthesis (ACCα, SCD, FABP1, and DGAT2) at three weeks. Furthermore, the expression of hepatic DGAT1/DGAT2 was sustained at six months, concomitant with mitochondrial dysfunction (i.e., elevated p66shc) and oxidative stress. Interest-ingly, decreases in miR‐203a‐3p and miR‐29a/b/c, both implicated in dyslipidemia, were also observed in these Δ9‐THC‐exposed offspring. Collectively, these findings indicate that prenatal Δ9‐ THC exposure results in long‐term dyslipidemia associated with enhanced hepatic lipogenesis. This is attributed by mitochondrial dysfunction and epigenetic mechanisms

New insight into the role of the β3 subunit of the GABAA-R in development, behavior, body weight regulation, and anesthesia revealed by conditional gene knockout

<p>Abstract</p> <p>Background</p> <p>The β3 subunit of the γ-aminobutyric acid type A receptor (GABA_A-R) has been reported to be important for palate formation, anesthetic action, and normal nervous system function. This subunit has also been implicated in the pathogenesis of Angelman syndrome and autism spectrum disorder. To further investigate involvement of this subunit, we previously produced mice with a global knockout of β3. However, developmental abnormalities, compensation, reduced viability, and numerous behavioral abnormalities limited the usefulness of that murine model. To overcome many of these limitations, a mouse line with a conditionally inactivated β3 gene was engineered.</p> <p>Results</p> <p>Gene targeting and embryonic stem cell technologies were used to create mice in which exon 3 of the β3 subunit was flanked by loxP sites (i.e., floxed). Crossing the floxed β3 mice to a cre general deleter mouse line reproduced the phenotype of the previously described global knockout. Pan-neuronal knockout of β3 was achieved by crossing floxed β3 mice to Synapsin I-cre transgenic mice. Palate development was normal in pan-neuronal β3 knockouts but ~61% died as neonates. Survivors were overtly normal, fertile, and were less sensitive to etomidate. Forebrain selective knockout of β3 was achieved using α CamKII-cre transgenic mice. Palate development was normal in forebrain selective β3 knockout mice. These knockouts survived the neonatal period, but ~30% died between 15–25 days of age. Survivors had reduced reproductive fitness, reduced sensitivity to etomidate, were hyperactive, and some became obese.</p> <p>Conclusion</p> <p>Conditional inactivation of the β3 gene revealed novel insight into the function of this GABA_A-R subunit. The floxed β3 knockout mice described here will be very useful for conditional knockout studies to further investigate the role of the β3 subunit in development, ethanol and anesthetic action, normal physiology, and pathophysiologic processes.</p

The role of discharge variability in determining alluvial stratigraphy

We illustrate the potential for using physics-based modeling to link alluvial stratigraphy to large river morphology and dynamics. Model simulations, validated using ground penetrating radar data from the Río Paraná, Argentina, demonstrate a strong relationship between bar-scale set thickness and channel depth, which applies across a wide range of river patterns and bar types. We show that hydrologic regime, indexed by discharge variability and flood duration, exerts a first-order influence on morphodynamics and hence bar set thickness, and that planform morphology alone may be a misleading variable for interpreting deposits. Indeed, our results illustrate that rivers evolving under contrasting hydrologic regimes may have very similar morphology, yet be characterized by marked differences in stratigraphy. This realization represents an important limitation on the application of established theory that links river topography to alluvial deposits, and highlights the need to obtain field evidence of discharge variability when developing paleoenvironmental reconstructions. Model simulations demonstrate the potential for deriving such evidence using metrics of paleocurrent variance

On SIC-POVMs in Prime Dimensions

The generalized Pauli group and its normalizer, the Clifford group, have a rich mathematical structure which is relevant to the problem of constructing symmetric informationally complete POVMs (SIC-POVMs). To date, almost every known SIC-POVM fiducial vector is an eigenstate of a "canonical" unitary in the Clifford group. I show that every canonical unitary in prime dimensions p > 3 lies in the same conjugacy class of the Clifford group and give a class representative for all such dimensions. It follows that if even one such SIC-POVM fiducial vector is an eigenvector of such a unitary, then all of them are (for a given such dimension). I also conjecture that in all dimensions d, the number of conjugacy classes is bounded above by 3 and depends only on d mod 9, and I support this claim with computer computations in all dimensions < 48.Comment: 6 pages, no figures. v3 Refs added, improved discussion of previous work. Ref to a proof of the main conjecture also adde

Clinical, biochemical, and genetic spectrum of seven patients with NFU1 deficiency

Disorders of the mitochondrial energy metabolism are clinically and genetically heterogeneous. An increasingly recognized subgroup is caused by defective mitochondrial iron-sulfur (Fe-S) cluster biosynthesis, with defects in 13 genes being linked to human disease to date. Mutations in three of them, NFU1, BOLA3, and IBA57, affect the assembly of mitochondrial [4Fe-4S] proteins leading to an impairment of diverse mitochondrial metabolic pathways and ATP production. Patients with defects in these three genes present with lactic acidosis, hyperglycinemia, and reduced activities of respiratory chain complexes I and II, the four lipoic acid-dependent 2-oxoacid dehydrogenases and the glycine cleavage system (GCS). To date, five different NFU1 pathogenic variants have been reported in 15 patients from 12 families. We report on seven new patients from five families carrying compound heterozygous or homozygous pathogenic NFU1 mutations identified by candidate gene screening and exome sequencing. Six out of eight different disease alleles were novel and functional studies were performed to support the pathogenicity of five of them. Characteristic clinical features included fatal infantile encephalopathy and pulmonary hypertension leading to death within the first 6 months of life in six out of seven patients. Laboratory investigations revealed combined defects of pyruvate dehydrogenase complex (five out of five) and respiratory chain complexes I and II+III (four out of five) in skeletal muscle and/or cultured skin fibroblasts as well as increased lactate (five out of six) and glycine concentration (seven out of seven). Our study contributes to a better definition of the phenotypic spectrum associated with NFU1 mutations and to the diagnostic workup of future patients

Microwave Spectroscopy of Thermally Excited Quasiparticles in YBa_2Cu_3O_{6.99}

We present here the microwave surface impedance of a high purity crystal of $YBa_2Cu_3O_{6.99}$ measured at 5 frequencies between 1 and 75 GHz. This data set reveals the main features of the conductivity spectrum of the thermally excited quasiparticles in the superconducting state. Below 20 K there is a regime of extremely long quasiparticle lifetimes, due to both the collapse of inelastic scattering below $T_c$ and the very weak impurity scattering in the high purity $BaZrO_3$-grown crystal used in this study. Above 20 K, the scattering increases dramatically, initially at least as fast as $T^4$.Comment: 13 pages with 10 figures. submitted to Phys Rev

Three-dimensional modelling of a very large river the Río Paraná

River hydrodynamicsBed roughness and flow resistanc

Microwave Electrodynamics of Electron-Doped Cuprate Superconductors

We report microwave cavity perturbation measurements of the temperature dependence of the penetration depth, lambda(T), and conductivity, sigma(T) of Pr_{2-x}Ce_{x}CuO_{4-delta} (PCCO) crystals, as well as parallel-plate resonator measurements of lambda(T) in PCCO thin films. Penetration depth measurements are also presented for a Nd_{2-x}Ce_{x}CuO_{4-delta} (NCCO) crystal. We find that delta-lambda(T) has a power-law behavior for T<T_c/3, and conclude that the electron-doped cuprate superconductors have nodes in the superconducting gap. Furthermore, using the surface impedance, we have derived the real part of the conductivity, sigma_1(T), below T_c and found a behavior similar to that observed in hole-doped cuprates.Comment: 4 pages, 4 figures, 1 table. Submitted to Physical Review Letters revised version: new figures, sample characteristics added to table, general clarification give