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Using weekly music charts data in 10 countries over the period 1990–2015, we analyze whether digitization leads to a trend of homogenization of music content or conversely to a greater acoustic disparity. We split the digitization era in four periods that correspond to four new emblematic distribution models (Napster, iTunes, YouTube, Spotify). Our main result is that while acoustic diversity decreased during the iTunes and the YouTube periods, the period that begins with the introduction of audio streaming services, such as Spotify, represents a turning point and is marked by a significant increase in acoustic diversity. [ABSTRACT FROM AUTHOR]

Intraperitoneal insulin allows physiological portal insulin administration and first-pass hepatic insulin extraction, but the impact on liver metabolism and inflammation is unknown. Our objective was to compare the impact, on metabolic control and liver function, of the same dose of insulin administered either intraperitoneally or subcutaneously during continuous infusion in diabetic rats. Wistar rats were randomly divided into 4 groups: control (C), untreated diabetic (streptozotocin, 100 mg/kg) and diabetic rats treated by continual subcutaneous Insuplant® infusion ( CSII) and continual intraperitoneal Insuplant® infusion ( CPII) of 2 UI/200 g/day (via an osmotic mini-pump for 1-4 weeks). Insulin signalling pathways were analysed through hepatic expression of growth hormone receptor and phosphorylated insulin receptor substrate 1. Metabolic control was determined by measurement of body weight, blood glucose and fructosamine. Liver function was assessed by measuring insulin-like growth factor-1 ( IGF-1), with global inflammation assessed by levels of alpha-2-macroglobulin (α2M) and lipid peroxidation in plasma. Liver inflammation was evaluated by quantification of hepatic macrophage infiltration and reactive oxygen species production. CPII induced a better improvement in metabolic control and liver function than CSII, producing a significant decrease in blood glucose and fructosamine, coupled with increased IGF-1 and hepatic glycogen storage. Moreover, liver oxidative stress and liver inflammation were reduced. Such observations indicate that the same insulin level in CPII improves glucose control and hepatic glucose metabolism and function, attenuating the hepatic inflammatory response to diabetes. These data demonstrate the importance of focusing on therapeutics to allow first-pass hepatic insulin extraction or prevent diabetic complications. [ABSTRACT FROM AUTHOR]

The anti-inflammatory effects of CI-1044 and of the other selective PDE4 inhibitors rolipram and cilomilast were investigated in Brown-Norway (BN) rats, against lipopolysaccharide-induced tumor necrosis factor α (TNFα) production in whole blood and antigen-induced lung eosinophilia. In vitro, CI-1044 inhibited TNFα production with an IC50 of 0.31 μm being equipotent to Cilomilast (IC50 = 0.26 μm) and rolipram (IC50 = 0.11 μm). Given orally, CI-1044 inhibited ex vivo TNFα production with an ED50 value of 0.4 mg/kg after single administration, whereas rolipram (ED50 = 1.4 mg/kg) and cilomilast (ED50 = 1.6 mg/kg) were less potent. In the same ex vivo setting, but given repeatedly, CI-1044 led to an ED50 of 0.5 mg/kg corresponding to a plasma concentration of 82.6 ng/mL (0.22 μm). In vivo, CI-1044 prevented TNFα release with an ED50 of 1 mg/kg p.o. and inhibited ovalbumin-induced lung eosinophilia following single or repeated oral administration with an ED50 of 3.25 and 4.8 mg/kg p.o., respectively, suggesting the absence of pharmacological tolerance. CI-1044 in this model was equipotent to rolipram (81% inhibition at 10 mg/kg) but better than cilomilast (25% inhibition at 10 mg/kg). Finally, CI-1044 (10 mg/kg) inhibited inflammatory cell recruitment with a long duration of action (up to 8 h) and was still active when given post-challenge. Our data show that CI-1044 is an orally active PDE4 inhibitor that may be used as an anti-inflammatory therapy in lung inflammatory diseases. [ABSTRACT FROM AUTHOR]

Objective It is unknown why some patients with biochemical evidence of primary aldosteronism (PA) do not develop hypertension. We aimed to compare clinical and biochemical characteristics of normotensive and hypertensive patients with PA. Design and patients Retrospective comparison of 10 normotensive and 168 hypertensive patients with PA for office or ambulatory blood pressure, serum potassium, plasma aldosterone and renin concentrations; the aldosterone : renin ratio, and tumour size. Comparison of initial hormonal pattern and drop in blood pressure following adrenalectomy in five normotensive and nine hypertensive patients matched for age, sex and body mass index. Results The 10 normotensive patients were women and presented with hypokalemia or an adrenal mass. Age, plasma aldosterone and renin concentrations were similar in normotensive and hypertensive cases, but kalemia and body mass index were significantly lower in the normotensive patients. Mean tumour diameter was larger in the normotensive patients than in the hypertensive matched patients with an adenoma ( P < 0·01). In normotensive patients, diastolic blood pressure and upright aldosterone correlated negatively with kalemia. Blood pressure was lowered similarly after adrenalectomy in five normotensive PA patients and in their matched hypertensive counterparts. Aldosterone synthase expression was detected in four out of five adrenal tumours. Conclusions Blood pressure may be normal in patients with well-documented PA. The occurrence of hypokalemia, despite a normal blood pressure profile, suggests that protective mechanisms against hypertension are present in normotensive patients. [ABSTRACT FROM AUTHOR]

Adenine phosphoribosyltransferase (APT; EC 2.4.2.7) is a constitutively expressed enzyme involved in the one-step salvage of adenine to AMP. The Arabidopsis thaliana genome contains five sequences annotated as encoding APT or APT-like enzymes. Three of these have now been cloned, over-expressed and compared using kinetic analyses. At a cytosolic pH, all bind adenine efficiently based on their Km values (0.8–2.6 µM ), although APT1 metabolizes adenine at a rate 31–53 times faster than APT2 and APT3, respectively. Since APT also has a possible role in the interconversion of cytokinin bases to nucleotides, we characterized the activity of each isoform on zeatin, isopentenyladenine and benzyladenine. Based on their Km values, APT2 and APT3 had much higher affinities than APT1 for all three cytokinins (15–440 µM for APT2 and 3 vs. 1.8–2.5 mM for APT1); conversely the Vmax values for APT2 and APT3 on these CK substrates showed the opposite trend, being 4- to 19-fold lower than those of APT1. Anti-peptide antibodies for APT1, APT2, and APT3 were prepared and used to examine the subcellular localization of each isoform. Based on these results, APT1 and APT3 appear to be cytosolic, while the localization of APT2 was inconclusive although sequence analysis implies that APT2 is also cytosolic. Each isoform was modelled against the crystal structure of APT from Leishmania donovani , and structural differences in substrate specificity-determining domains have been found. The estimated kinetic activities of these APTs suggest that they contribute primarily to adenine recycling, although an involvement in cytokinin interconversion cannot be discounted. [ABSTRACT FROM AUTHOR]

Two main aspects of the lipid dynamics, local microviscosity and lateral diffusion, were investigated in intact plant mitochondria isolated from different tissues exhibiting large differences in their fatty acids in terms of unsaturation (amount of linoleic and linolenic acids) or length of the hydrocarbon chains. In addition, the same parameters were determined in the outer and inner membranes isolated from cauliflower mitochondria, which differed not only in the fatty acid composition but also by the lipid-to-protein ratio. In intact mitochondria, local microviscosity assayed with anthroyloxy-fatty acids exhibited a transverse gradient from the surface to the center of the bilayer, which was mainly affected by the unsaturation index and the content in linoleic or linolenic acids. In contrast, lipid lateral diffusion increased as the content in linolenic or palmitic acids increased, but was not directly correlated to the unsaturation index. Interestingly, local microviscosity at the membrane surface was higher in the outer membrane than in the inner membrane, whereas no significant difference was found in lipid lateral diffusion. These results indicate that the influence of the fatty acid composition of mitochondrial membranes on the dynamics of the phospholipid bilayer depends on the type of movement considered and suggest that other parameters, such as the protein content of the bilayer, also affect membrane fluidity. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusions Sonothrombolysis is a potential adjunctive therapy for large vessel occlusion (LVO) stroke. Bedside ultrasound image‐guided high‐intensity focused ultrasound (HIFU) therapy could deliver higher energy therapeutic ultrasound to the thrombus with higher precision than what was previously accomplished in human trials. The aim is to test the feasibility of diagnostic transcranial contrast‐enhanced ultrasound (CEUS) to image the occlusion site and continuously maintain the guidance image on‐target for a sufficient exposure time for HIFU to be effective during LVO stroke evaluation and treatment.This prospective, single center, observational cohort study included adult patients, presenting within 6 hours of stroke symptom onset, with LVO identified on computed tomography angiography (CTA). A hand‐held CEUS imaging study was initiated following CTA and lasted up to 30 minutes. The primary outcome is the proportion of patients where a guidance CEUS image of the occlusion was achieved.A CEUS image of the occluded artery was obtained in 32/35 of the included patients. The median total imaging time was 23 minutes (interquartile range 15‐30). Patients undergoing thrombectomy had a lower total imaging time (17 vs. 29.5 minutes, p = .002). When imaging was successful, on‐target image was maintained for only 58% (standard deviation 23.8%) of total imaging time. No complications related to CEUS were observed.This feasibility study explored the use of diagnostic transcranial CEUS for continuous imaging of occlusion sites in LVO strokes. Challenges in maintaining target image during HIFU were identified, highlighting the need for technical advances for clinical application. [ABSTRACT FROM AUTHOR]