The Greatwall–Endosulfine Switch Accelerates Autophagic Flux during the Cell Divisions Leading to G1 Arrest and Entry into Quiescence in Fission Yeast

Entry into quiescence in the fission yeast Schizosaccharomyces pombe is induced by nitrogen starvation. In the absence of nitrogen, proliferating fission yeast cells divide twice without cell growth and undergo cell cycle arrest in G1 before becoming G0 quiescent cells. Under these conditions, autophagy is induced to produce enough nitrogen for the two successive cell divisions that take place before the G1 arrest. In parallel to the induction of autophagy, the Greatwall–Endosulfine switch is activated upon nitrogen starvation to down-regulate protein phosphatase PP2A/B55 activity, which is essential for cell cycle arrest in G1 and implementation of the quiescent program. Here we show that, although inactivation of PP2A/B55 by the Greatwall–Endosulfine switch is not required to promote autophagy initiation, it increases autophagic flux at least in part by upregulating the expression of a number of autophagy-related genes.     

Brown Adipose Tissue Sheds Extracellular Vesicles That Carry Potential Biomarkers of Metabolic and Thermogenesis Activity Which Are Affected by High Fat Diet Intervention

Brown adipose tissue (BAT) is a key target for the development of new therapies against obesity due to its role in promoting energy expenditure; BAT secretory capacity is emerging as an important contributor to systemic effects, in which BAT extracellular vesicles (EVs) (i.e., batosomes) might be protagonists. EVs have emerged as a relevant cellular communication system and carriers of disease biomarkers. Therefore, characterization of the protein cargo of batosomes might reveal their potential as biomarkers of the metabolic activity of BAT. In this study, we are the first to isolate batosomes from lean and obese Sprague–Dawley rats, and to establish reference proteome maps. An LC-SWATH/MS analysis was also performed for comparisons with EVs secreted by white adipose tissue (subcutaneous and visceral WAT), and it showed that 60% of proteins were exclusive to BAT EVs. Precisely, batosomes of lean animals contain proteins associated with mitochondria, lipid metabolism, the electron transport chain, and the beta-oxidation pathway, and their protein cargo profile is dramatically affected by high fat diet (HFD) intervention. Thus, in obesity, batosomes are enriched with proteins involved in signal transduction, cell communication, the immune response, inflammation, thermogenesis, and potential obesity biomarkers including UCP1, Glut1, MIF, and ceruloplasmin. In conclusion, the protein cargo of BAT EVs is affected by the metabolic status and contains potential biomarkers of thermogenesis activity.     

The shift from recency to primacy with increasing delay.

Five experiments examined the recency–primacy shift in which memory for early list items improves and memory for later items becomes worse as the delay between study and test increases. Experiment 1 replicated the shift in a recognition task in which the physical form of the study and test items differed, ruling out an explanation that invokes visual memory. Experiment 2 observed the change when only 1 serial position was tested, eliminating an explanation based on changing strategies or proactive interference. Experiment 3 showed a similar change from recency to primacy when the to-be-remembered stimuli were auditory. Experiments 4 and 5 demonstrated that the same recency–primacy trade-off occurs for words in a sentence. Although it is possible to offer piecemeal explanations for each experiment, the dimensional distinctiveness model accounts for the results in each of the 5 experiments in exactly the same way. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterizing the viscoelastic properties of thin hydrogel-based constructs for tissue engineering applications.

We present a novel indentation method for characterizing the viscoelastic properties of alginate and agarose hydrogel based constructs, which are often used as a model system of soft biological tissues. A sensitive long working distance microscope was used for measuring the time-dependent deformation of the thin circular hydrogel membranes under a constant load. The deformation of the constructs was measured laterally. The elastic modulus as a function of time can be determined by a large deformation theory based on Mooney-Rivlin elasticity. A viscoelastic theory, Zener model, was applied to correlate the time-dependent deformation of the constructs with various gel concentrations, and the creep parameters can therefore be quantitatively estimated. The value of Young's modulus was shown to increase in proportion with gel concentration. This finding is consistent with other publications. Our results also showed the great capability of using the technique to measure gels with incorporated corneal stromal cells. This study demonstrates a novel and convenient technique to measure mechanical properties of hydrogel in a non-destructive, online and real-time fashion. Thus this novel technique can become a valuable tool for soft tissue engineering.     

Pituitary enlargement due to primary hypothyroidism: growth hormone response to GHRH, GHRP-6 and GHRH plus GHRP-6

While intake of clear fluids 2-3 h before surgery is considered safe as it does not influence gastric content, it is not known if the same applies to a light breakfast meal. We therefore studied gastric emptying of a light breakfast in healthy, female volunteers without evidence of gastrointestinal motility disorders. The test meal consisted of one slice of buttered toast with jam, one cup of coffee without milk or sugar and one glass of pulp-free orange juice taken together with a paracetamol mixture. Using gastric ultrasonography, the stomach was identified without problems in all subjects, and gastric emptying curves using changes in gastric antral area and serum-paracetamol were obtained. Emptying of the fluid phase started immediately after intake of the meal. All subjects had solid particles in the stomach 120 min after the meal, 3 patients were considered empty after 180 min, 6 after 210 min and all after 240 min. The gastric antral area returned to fasting value significantly faster than the disappearance of solid particles; median 150 min versus 210 min; P = 0.01. Our results show that in healthy subjects the stomach cannot be considered empty for solid particles the first 4 h after a light breakfast meal. To secure some safety limits, we suggest a 6-h mandatory preoperative fast after a light breakfast.     

Lipid binding properties of a factor necessary for linoleic acid desaturation

Suspension and centrifugation of crude microsomes of rat liver in low ionic strength solution separated a soluble protein fraction that is necessary for the full activity of the linoleic acid desaturase. The fraction partially purified through Sephadex G-150 still retains lipids which are mainly constituted by phosphatidylcholine. Linoleic acid predominates in the fatty acid composition. By NaCl gradient centrifugation and electrophoresis in gelatinized cellulose acetate, the factor behaves like a lipoprotein. The factor binds linoleic acid and linolyl-CoA that are desaturated to γ-linolenic acid when incubated with washed microsomes. Albumin does not replace the factor.     

Leptin inhibits in vitro hypothalamic somatostatin secretion and somatostatin mRNA levels

Leptin, the product of the ob gene, is a recently discovered hormone secreted by adipocytes that regulates food intake and energy expenditure. The site of action of leptin is likely to be the hypothalamus, since this area is important in the control of food intake and leptin receptor mRNA is particularly abundant in this area. In order to further unravel the mechanisms by which leptin acts, we have studied the effect of leptin on in vitro somatostatin synthesis and secretion. Leptin administration to fetal rat neurones in monolayer culture led to a time dependent decrease in basal somatostatin secretion and somatostatin mRNA levels, the maximal effect being observed with 6x10(-8) M leptin after 24 h incubation. Furthermore, leptin completely blunted 10(-7) M Neuropeptide Y-induced increase in somatostatin secretion and somatostatin mRNA levels as well as 10(-3) M (Bu)2-cAMP and 10(-6) M A23187-induced somatostatin secretion. Finally, leptin (3x10(-8) M M) also inhibited low glucose (1.1 mM) induced-somatostatin secretion in perifused adult hypothalami. This data indicates that leptin can influence the neuroendocrine system by regulating hypothalamic somatostatin gene expression.     

Right hematocolpos and hematometra with left renal agenesis. A rare association. Apropos a case

Although this anomaly is seen more frequently, the present case is unique in that the genital anomaly (imperforate vagina with the subsequent hematocolpos and hematometra) was associated with contralateral renal agenesis, whereas the cases reported in the literature have all been ipsilateral. Like most of the cases, the presenting symptom was acute urinary retention arising from extrinsic compression of the genital mass on the lower urinary tract. The embryological aspects of the genitourinary system concerning the present case are discussed, as well as some of the hypotheses that have been put forward to explain the etiology of these anomalies, although these have been developed on the basis of the associated ipsilateral anomalies observed.     

Angiotensin II type 1 receptor A1166C gene polymorphism and essential hypertension in San Luis.

Essential hypertension is considered a multifactorial trait resulting from a combination of environmental and genetic factors. The angiotensin II type 1 receptor mediates the vasoconstrictor and growth-promoting effects of Ang II. The A1166C polymorphism of the AT1 receptor gene may be associated with cardiovascular phenotypes, such as high arterial blood pressure, aortic stiffness, and increased cardiovascular risk. We investigated the association between this A1166C polymorphism and hypertension in hypertense and normotense subjects from San Luis (Argentina) by mismatch PCR-RFLP analysis. Hypertense patients exhibited significant increases in lipid related values and body mass index. The frequency of occurrence of the C1166 allele was higher among patients with hypertension (0.19) than in the control group (0.06). No significant association was found between this polymorphism and essential hypertension in the study population, although the AC genotype prevalence was higher in patients with hypertension and positive family history of hypertension (32%) than in control subjects (12%). Patients with the A1166C polymorphism exhibited higher levels of serum total cholesterol, LDL-cholesterol and BMI than in control subjects. Taken together the genotype and biochemical parameters and considering the restrictive selection criteria used, the present results suggest a correlation between AT1 A1166C gene polymorphism and risk of cardiovascular disease.