The suprachiasmatic nucleus (SCN) acts as the central clock to coordinate circadian oscillations in mammalian behavior, physiology and gene expression. Despite our knowledge of the circadian transcriptome of the SCN, how it impacts genome-wide protein expression is not well understood. Here, we interrogated the murine SCN proteome across the circadian cycle using SILAC-based quantitative mass spectrometry. Of the 2112 proteins that were accurately quantified, 20% (421 proteins) displayed a time-of-day-dependent expression profile. Within this time-of-day proteome, 11% (48 proteins) were further defined as circadian based on a sinusoidal expression pattern with a ∼24 h period. Nine circadianly expressed proteins exhibited 24 h rhythms at the transcript level, with an average time lag that exceeded 8 h. A substantial proportion of the time-of-day proteome exhibited abrupt fluctuations at the anticipated light-to-dark and dark-to-light transitions, and was enriched for proteins involved in several key biological pathways, most notably, mitochondrial oxidative phosphorylation. Additionally, predicted targets of miR-133ab were enriched in specific hierarchical clusters and were inversely correlated with miR133ab expression in the SCN. These insights into the proteomic landscape of the SCN will facilitate a more integrative understanding of cellular control within the SCN clock.

The circadian clock is an endogenous oscillator that drives daily rhythms in physiology, behavior, and gene expression. The underlying mechanisms of circadian timekeeping are cell-autonomous and involve oscillatory expression of core clock genes that is driven by interconnecting transcription-translation feedback loops (TTFLs). Circadian clock TTFLs are further regulated by posttranslational modifications, in particular, phosphorylation. The hippocampus plays an important role in spatial memory and the conversion of short-to long-term memory. Several studies have reported the presence of a peripheral oscillator in the hippocampus and have highlighted the importance of circadian regulation in memory formation. Given the general importance of phosphorylation in circadian clock regulation, we performed global quantitative proteome and phosphoproteome analyses of the murine hippocampus across the circadian cycle, applying spiked-in labeled reference and high accuracy mass spectrometry (MS). Of the 3,052 proteins and 2,868 phosphosites on 1,368 proteins that were accurately quantified, 1.7% of proteins and 5.2% of phosphorylation events exhibited time-of-day-dependent expression profiles. The majority of circadian phosphopeptides displayed abrupt fluctuations at mid-to-late day without underlying rhythms of protein abundance. Bioinformatic analysis of cyclic phosphorylation events revealed their diverse distribution in different biological pathways, most notably, cytoskeletal organization and neuronal morphogenesis. This study provides the first large-scale, quantitative MS analysis of the circadian phosphoproteome and proteome of the murine hippocampus and highlights the significance of rhythmic regulation at the posttranslational level in this peripheral oscillator. In addition to providing molecular insights into the hippocampal circadian clock, our results will assist in the understanding of genetic factors that underlie rhythms-associated pathological states of the hippocampus.

No abstract

No abstract

Background: Idiopathic intracranial hypertension (IIH) is a rare condition typically affecting women with obesity who are of child-bearing age. Patients commonly present with headaches, visual disturbances, pulsatile tinnitus and papilledema. The association between IIH and obesity has been well established in the literature, suggesting that weight loss may contribute to improving IIH. For patients with severe obesity for whom conservative management is not successful, bariatric surgery is an effective modality for weight loss. We aimed to systematically review the literature to determine the efficacy of bariatric surgery in the treatment of IIH Methods: We conducted a comprehensive search of MEDLINE, Embase, Scopus, the Cochrane Library and Web of Science (limited to studies in humans published in English between January 1946 and July 2015).Results: Twelve primary studies (n = 39 patients) were included in the systematic review. All patients had a preoperative diagnosis of IIH. Preoperative body mass index (BMI) was 47.4 ± 3.6 kg/m 2 ; BMI improved to 33.7 ± 2.1 kg/m 2 and 33.9 ± 11.6 kg/m 2 at 6 and 12 months postoperatively, respectively. Lumbar puncture opening pressures decreased from 34.4 ± 6.9 cm H 2 O to 14.0 ± 3.6 cm H 2 O after surgery. Common symptoms of IIH improved after bariatric surgery: headaches (100% preoperatively v. 10% postoperatively), visual complaints (62% v. 44%), tinnitus (56% v. 3%) and papilledema (62% v. 8%). Conclusion:Bariatric surgery appears to lead to considerable improvement in IIH. Idiopathic intracranial hypertension is not a well-publicized comorbidity of obesity, but its presence may be considered as an indication for bariatric surgery.Contexte : L'hypertension intracrânienne (HTIC) idiopathique est une affection rare qui touche surtout les femmes atteintes d'obésité en âge de procréer. Les symptômes courants sont des maux de tête, des troubles de la vue, des acouphènes pulsatiles et un oedème papillaire. Le lien entre l'HTIC idiopathique et l'obésité est bien établi dans la littérature, ce qui suggère que la perte de poids pourrait améliorer le tableau clinique de l'HTIC. Pour les patients atteints d'obésité sévère pour lesquels le traitement conservateur ne fonctionne pas, la chirurgie bariatrique est un moyen efficace de perdre du poids. Cette revue systématique de la littérature vise à déterminer l'efficacité de la chirurgie bariatrique dans le traitement de l'HTIC idiopathique.Méthodes : Nous avons interrogé MEDLINE, Embase, Scopus, la Bibliothèque Cochrane et Web of Science (limites : études portant sur les humains publiées en anglais entre janvier 1946 et juillet 2015).Résultats : Douze études primaires (n = 39 patients) ont été incluses dans la revue systématique. Tous les patients avaient un diagnostic préopératoire d'HTIC idiopathique. L'indice de masse corporelle (IMC) préopératoire était de 47,4 ± 3,6 kg/m 2 ; l'IMC est passé à 33,7 ± 2,1 kg/m 2 6 mois après l'opération, puis à 33,9 ± 11,6 kg/m 2 12 mois après l'opération. Les pressions d'ouverture des ponctions ...

No abstract

No abstract

No abstract