In vivo characterization of the circadian clock output gene usp2

Life on earth is subject to the repeated change between day and night periods. All organisms that undergo these alterations have to anticipate consequently the adaptation of their physiology and possess an endogenous periodicity of about 24 hours called circadian rhythm from the Latin circa (about) and diem (day). At the molecular level, virtually all cells of an organism possess a molecular clock which drives rhythmic gene expression and output functions. Besides altered rhythmicity in constant conditions, impaired clock function causes pathophysiological conditions such as diabetes or hypertension. These data unveil a part of the mechanisms underlying the well-described epidemiology of shift work and highlight the function of clock-driven regulatory mechanisms. The post-translational modification of proteins by the ubiquitin polypeptide is a central mechanism to regulate their stability and activity and is capital for clock function. Similarly to the majority of biological processes, it is reversible. Deubiquitylation is carried out by a wide variety of about ninety deubiquitylating enzymes and their function remains poorly understood, especially in vivo. This class of proteolytic enzymes is parted into five families including the Ubiquitin-Specific Proteases (USP), which is the most important with about sixty members. Among them, the Ubiquitin-Specific Protease 2 (Usp2) gene encodes two protein isoforms, USP2-45 and USP2-69. The first is ubiquitously expressed under the control of the circadian clock and displays all features of core clock genes or its closest outputs effectors. Additionally, Usp2-45 was also found to be induced by the mineralocorticoid hormone aldosterone and thought to participate in Na+ reabsorption and blood pressure regulation by Epithelial Na+ Channel ENaC in the kidneys. During my thesis, I aimed to characterize the role of Usp2 in vivo with respect to these two areas, by taking advantage of a total constitutive knockout mouse model. In the first project I aimed to validate the role of USP2-45 in Na+ homeostasis and blood pressure regulation by the kidneys. I found no significant alterations of diurnal Na+ homeostasis and blood pressure in these mice, indicating that Usp2 does not play a substantial role in this process. In urine analyses, we found that our Usp2-KO mice are actually hypercalciuric. In a second project, I aimed to understand the causes of this phenotype. I found that the observed hypercalciuria results essentially from intestinal hyperabsorption. These data reveal a new role for Usp2 as an output effector of the circadian clock in dietary Ca2+ metabolism in the intestine.

Mrs Powers sur un éléphant [de la troupe des Powers elephants] à New-York : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58885

Un éléphant de cirque [de la troupe des Powers elephants] à New-York : [photographie de presse] / [Agence Rol]

Référence bibliographique : Rol, 58886

1.° Liber cujus titulus : Potestas divitiarum illuminati Doctoris Raymundi Lullii de Insula Majoricarum, divini Philosophi, de compositione lapidis philosophici benedicti : et in eo est optima expositio testamenti Hermetis, patris omnium Alkimistarum. — 2.° Ejusdem clavicula continens scientiam et praxim magisterii philosophici. — 3.° Apologia domni Placidi de Novo, Monachi sancti Benedicti, pro aequè catholica ac piissima Lulliana doctrina ; ad Paulum V. Pontificem maximum. — 4.° Anonymi tractatus de rebus ad alchymiam pertinentibus : italicè.

Baluzianus

Report of the Committee on Military Affairs, on the differences that exist, between the United States and some of the individual States, respecting the relative powers of the general and state governments over the militia.--

February 28, 1815. Printed by order of the Senate of the United States.

Report of the Committee on Military Affairs, on the differences that exist, between the United States and some of the individual States, respecting the relative powers of the general and state governments over the militia

February 28, 1815. Printed by order of the Senate of the United States. Printed be Roger C. Weightman

The Effect of Trainer Muscularity and Expertise on Self-Presentational Concerns, Body Image, and Performance in College Men during One-Repetition Maximum Testing

This study attempted to manipulate self-presentational efficacy to examine the effect on social anxiety, social physique anxiety, drive for muscularity, and maximal strength performance during a one-repetition maximum (1-RM) chest press and leg press test. Ninety-nine college men with a minimum of six months of previous weight training experience were randomly assigned to complete a 1-RM protocol with either a muscular male trainer described as an expert or a lean male trainer described as a novice. Participants completed measures of self-presentation and body image prior to meeting their respective trainer, and following the completion of the 1-RM tests. Although the self-presentational efficacy manipulation was not successful, the trainers were perceived significantly differently on musculature and expertise. The group with the muscular, expert trainer reported higher social anxiety and attained higher 1-RM scores for the chest and leg press. Thus, trainer characteristics can affect strength performance and self-presentational concerns in this population.

Micromorphology of Last Glacial Maximum Grounding line sediments around the Antarctic Peninsula

Sediments recovered from seven Last Glacial Maximum grounding lines sites, around the Antarctic Peninsula, were analyzed using micromorphology. This is the first evidence that grounding line sediments from around the Antarctic Peninsula have complex deformational histories and subglacial origins. It was determined that grounding zone wedge contain multiple units, or diamicton layers, with homogenized boundaries. The multiple diamicton units / layers are due to the accretionary formation of a grounding line wedge. All the sediments were deposited via deformation, and continual reincorporation, homogenization of lower diamicton layers by upper diamicton layers produced what macroscopically appeared to be a single massive diamicton unit. The morainal ridge that was sampled, alternatively, is composed of a single unit, or diamicton layer, that was subglacial in origin and believed to have been pushed out to form a ridge that was subsequently deformed via glacial push.

Correlation of Protein Homeostasis With Maximum Lifespans in Endothermic Vertebrates

Cellular stress resistance has been shown to be highly correlated with longevity. However, the mechanisms conferring this stress resistance have yet to be identified. Maintenance of protein homeostasis is a critical component of cellular maintenance and stress resistance. Superior protein homeostasis capacities may thus underlie the greater stress resistance observed in longer-lived animals; however, little vertebrate data have been provided supporting this idea. I used two different experimental approaches to test the associations of protein homeostasis capacities with stress resistance and lifespan: 1) a comparison between a large set of vertebrate species with varying body masses and lifespans and 2) a comparison of long-lived Snell dwarf mice and their normal littermates. Protein homeostasis mechanisms including protein degradation activity, protein repair activity and molecular chaperone levels were examined. These measurements were performed in liver, heart and brain tissues, and isolated myoblasts. My results indicated that neither protein degradation nor protein repair were upregulated in association with enhanced stress resistance and longevity in an inter-species and intraspecies context. Furthermore, my results did show that there is a positive correlation between molecular chaperone levels and maximum lifespan (MLSP). However, there was no elevation of chaperone levels in the long-lived Snell dwarf mouse, indicating there are other mechanisms linked to their increased lifespan. Therefore, these results suggest that molecular chaperones are involved in increasing animal lifespan in an interspecies context.

[British Parliamentary papers], Session 24 November, 1812 - 22 July, 1813. Vol. XIV, Correspondence and treaties with foreign powers.

Most of this volume consists of correspondence between high ranking U.S. and British statesmen. E.g., James Madison, James Monroe, The Marquess Wellesley (brother of Arthur Wellesley, Duke of Wellington). The discussion centers around the War of 1812. Also includes facsimilies of treaties signed between Great Britain and Sweden, Russia and Sicily.

Reduced power output in skeletal muscles devoid of skMLCK: RLC phosphorylation contributes to peak performance

Regulatory light chain (RLC) phosphorylation in fast twitch muscle is catalyzed by skeletal myosin light chain kinase (skMLCK), a reaction known to increase muscle force, work, and power. The purpose of this study was to explore the contribution of RLC phosphorylation on the power of mouse fast muscle during high frequency (100 Hz) concentric contractions. To determine peak power shortening ramps (1.05 to 0.90 Lo) were applied to Wildtype (WT) and skMLCK knockout (skMLCK-/-) EDL muscles at a range of shortening velocities between 0.05-0.65 of maximal shortening velocity (Vmax), before and after a conditioning stimulus (CS). As a result, mean power was increased to 1.28 ± 0.05 and 1.11 ± .05 of pre-CS values, when collapsed for shortening velocity in WT and skMLCK-/-, respectively (n = 10). In addition, fitting each data set to a second order polynomial revealed that WT mice had significantly higher peak power output (27.67 ± 1.12 W/ kg-1) than skMLCK-/- (25.97 ± 1.02 W/ kg-1), (p < .05). No significant differences in optimal velocity for peak power were found between conditions and genotypes (p > .05). Analysis with Urea Glycerol PAGE determined that RLC phosphate content had been elevated in WT muscles from 8 to 63 % while minimal changes were observed in skMLCK-/- muscles: 3 and 8 %, respectively. Therefore, the lack of stimulation induced increase in RLC phosphate content resulted in a ~40 % smaller enhancement of mean power in skMLCK-/-. The increase in power output in WT mice suggests that RLC phosphorylation is a major potentiating component required for achieving peak muscle performance during brief high frequency concentric contractions.