Paleomagnetism of Jurassic Rocks in the Western Sierra Nevada Metamorphic Belt and its Bearing on the Structural Evolution of the Sierra Nevada Block

The western metamorphic belt of the Sierra Nevada consists of two eugeosynclinal terranes separated by the Melones and Sonora faults. Subvertical, bedded Mesozoic volcanic rocks metamorphosed to low greenschist facies predominate to the west, whereas Paleozoic metamorphic rocks of higher grade and greater structural complexity predominate to the east. In order to study the structural development of the faults, 121 samples of basalt and diabase were collected for paleomagnetic analysis from three Jurassic formations, the Logtown Ridge and Penon Blanco formations west of the Melones fault and the Sonora dike swarm to the east of the Sonora fault. A northwesterly, downward directed magnetization occurs in each unit. Three fold tests and a conglomerate test on the two formations west of the faults show that the magnetization is secondary, postdating Nevadan (Late Jurassic) folding and is probably coeval with peak metamorphism. An average of five paleomagnetic poles from the Sierra Nevada, three derived from the secondary magnetizations given herein and two previously published, all of probable Kimmeridgian age, yields λ′=67.2°N, ϕ′=161.2°E, and α95 =6.5°. Southeasterly magnetizations also occur in the Logtown Ridge Formation and Sonora dike swarm. Directions from the Sonora dikes are approximately antipodal to the secondary directions and are reversed; magnetizations from the Logtown Ridge Formation yield similar results only if corrected for the tilt of bedding. The Logtown Ridge magnetizations (tilt-corrected) yield a pole position near to that expected for North America. The data from the Sonora dikes require a tilt correction of 25°-30° toward the south-southwest about a horizontal axis parallel to the regional structure in order to yield a North American pole position. We conclude that the eastern wall rocks of the Melones and Sonora faults have been rotated 25°-30° in response to Nevadan deformation in contrast to the western wall rocks, which have been rotated about 90°

Plant ARGONAUTEs: Features, Functions and Unknowns

ARGONAUTEs (AGOs) are the effector proteins in eukaryotic small RNA(sRNA)– based gene silencing pathways controlling gene expression and transposon activity. In plants, AGOs regulate key biological processes such as development, response to stress, genome structure and integrity, and pathogen defense. Canonical functions of plant AGO–sRNA complexes include the endonucleolytic cleavage or translational inhibition of target RNAs, and the methylation of target DNAs. Here, I provide a brief update on the major features, molecular functions and biological roles of plant AGOs. A special focus is given to the more recent discoveries related to emerging molecular or biological functions of plant AGOs, as well as to the major unknowns in the plant AGO field.This work was supported by an Individual Fellowship from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No. 655841 to A.C.Carbonell Olivares, A. (2017). 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Design and development of a peptide-based adiponectin receptor agonist for cancer treatment

<p>Abstract</p> <p>Background</p> <p>Adiponectin, a fat tissue-derived adipokine, exhibits beneficial effects against insulin resistance, cardiovascular disease, inflammatory conditions, and cancer. Circulating adiponectin levels are decreased in obese individuals, and this feature correlates with increased risk of developing several metabolic, immunological and neoplastic diseases. Thus, pharmacological replacement of adiponectin might prove clinically beneficial, especially for the obese patient population. At present, adiponectin-based therapeutics are not available, partly due to yet unclear structure/function relationships of the cytokine and difficulties in converting the full size adiponectin protein into a viable drug.</p> <p>Results</p> <p>We aimed to generate adiponectin-based short peptide that can mimic adiponectin action and be suitable for preclinical and clinical development as a cancer therapeutic. Using a panel of 66 overlapping 10 amino acid-long peptides covering the entire adiponectin globular domain (residues 105-254), we identified the 149-166 region as the adiponectin active site. Three-dimensional modeling of the active site and functional screening of additional 330 peptide analogs covering this region resulted in the development of a lead peptidomimetic, ADP 355 (H-DAsn-Ile-Pro-Nva-Leu-Tyr-DSer-Phe-Ala-DSer-NH₂). In several adiponectin receptor-positive cancer cell lines, ADP 355 restricted proliferation in a dose-dependent manner at 100 nM-10 μM concentrations (exceeding the effects of 50 ng/mL globular adiponectin). Furthermore, ADP 355 modulated several key signaling pathways (AMPK, Akt, STAT3, ERK1/2) in an adiponectin-like manner. siRNA knockdown experiments suggested that ADP 355 effects can be transmitted through both adiponectin receptors, with a greater contribution of AdipoR1. <it>In vivo</it>, intraperitoneal administration of 1 mg/kg/day ADP 355 for 28 days suppressed the growth of orthotopic human breast cancer xenografts by ~31%. The peptide displayed excellent stability (at least 30 min) in mouse blood or serum and did not induce gross toxic effects at 5-50 mg/kg bolus doses in normal CBA/J mice.</p> <p>Conclusions</p> <p>ADP 355 is a first-in-class adiponectin receptor agonist. Its biological activity, superior stability in biological fluids as well as acceptable toxicity profile indicate that the peptidomimetic represents a true lead compound for pharmaceutical development to replace low adiponectin levels in cancer and other malignancies.</p

One day access to a running wheel reduces self-administration of d-methamphetamine, MDMA and methylone

BACKGROUND: Exercise influences drug craving and consumption in humans and drug self-administration in laboratory animals, but the effects can be variable. Improved understanding of how exercise affects drug intake or craving would enhance applications of exercise programs to human drug users attempting cessation. METHODS: Rats were trained in the intravenous self-administration (IVSA) of d-methamphetamine (METH; 0.05 mg/kg/inf), 3,4-methylenedioxymethamphetamine (MDMA; 0.5 mg/kg/inf) or methylone (0.5 mg/kg/inf). Once IVSA was established, the effect of ~22 hrs of wheel access in the home cage on subsequent drug taking was assessed in a two cohort crossover design. RESULTS: Provision of home cage wheel access during the day prior to IVSA sessions significantly decreased the self-administration of METH, MDMA and methylone. At the individual level, there was no correlation between the amount a rat used the wheel and the size of the individual’s decrease in drug intake. CONCLUSIONS: Wheel access can reduce self-administration of a variety of psychomotor stimulants. It does so immediately, i.e., without a need for weeks of exercise prior to drug access. This study therefore indicates that future mechanistic investigations should focus on acute effects of exercise. In sum, the results predict that exercise programs can be used to decrease stimulant drug use in individuals even with no exercise history and an established drug taking pattern