Pharmacologic Inhibition of the Anaphase-Promoting Complex Induces A Spindle Checkpoint-Dependent Mitotic Arrest in the Absence of Spindle Damage

SummaryMicrotubule inhibitors are important cancer drugs that induce mitotic arrest by activating the spindle assembly checkpoint (SAC), which, in turn, inhibits the ubiquitin ligase activity of the anaphase-promoting complex (APC). Here, we report a small molecule, tosyl-L-arginine methyl ester (TAME), which binds to the APC and prevents its activation by Cdc20 and Cdh1. A prodrug of TAME arrests cells in metaphase without perturbing the spindle, but nonetheless the arrest is dependent on the SAC. Metaphase arrest induced by a proteasome inhibitor is also SAC dependent, suggesting that APC-dependent proteolysis is required to inactivate the SAC. We propose that mutual antagonism between the APC and the SAC yields a positive feedback loop that amplifies the ability of TAME to induce mitotic arrest

Optical intra-day variability of the blazar S5 0716+714

We present an extensive recent multi-band optical photometric observations of the blazar S5 0716+714 carried out over 53 nights with two telescopes in India, two in Bulgaria, one in Serbia, and one in Egypt during 2019 November -- 2022 December. We collected 1401, 689, 14726, and 165 photometric image frames in B, V, R, and I bands, respectively. We montiored the blazar quasi-simultaneously during 3 nights in B, V, R, and I bands; 4 nights in B, V, and R; 2 nights in V, R, and I; 5 nights in B and R; and 2 nights in V and R bands. We also took 37 nights of data only in R band. Single band data are used to study intraday flux variability and two or more bands quasi-simultaneous observations allow us to search for colour variation in the source. We employ the power-enhanced F-test and the nested ANOVA test to search for genuine flux and color variations in the light curves of the blazar on intraday timescales. Out of 12, 11, 53, and 5 nights observations, intraday variations with amplitudes between ~3% and ~20% are detected in 9, 8, 31 and 3 nights in B, V, R, and I bands, respectively, corresponding to duty cycles of 75%, 73%, 58% and 60%. These duty cycles are lower than those typically measured at earlier times. On these timescales color variations with both bluer-when-brighter and redder-when-brighter are seen, though nights with no measurable colour variation are also present. We briefly discuss possible explanations for this observed intraday variability.Comment: 19 pages, 5 figures, 4 tables, Accepted for Publication in MNRA

Not Available

Not AvailableInulin and color imparting carotenoid pigments are candidate functional ingredients for development of a low-fat functional yoghurt. The study evaluates the potential of carotenoid-rich extract from red-capsicum (5%) and different levels of inulin (4, 6 and 8%) on functional and structural properties of low-fat setyoghurt. Changes in pH, syneresis, sensory and rheological parameters were monitored for 14 days at 662C. The variations in sensory acceptability and syneresis were related to rheological properties. Hysteresis area in the flow curve (shear stress–shear rate) increased until 10th day of storage. Inulin fortification significantly reduced syneresis by 59% over control. The time sweep and frequency sweep experiments confirmed stability of protein networks in yoghurt fortified with inulin at high levels. Consistency index of yoghurts was higher for inulin-fortified yoghurts and kept increasing up to 10 days. Results suggest promising applications of natural carotenoids in conjunction with inulin for improving quality of low-fat yoghurt.Not Availabl

Intragastric balloons in high-risk obese patients in a Brazilian center: initial experience

ABSTRACT Objective: to assess the short-term efficacy, tolerance and complications in high-risk morbidly obese patients treated with an intragastric balloon as a bridge for surgery. Methods: we conducted a post-hoc analysis study in a Brazilian teaching hospital from 2010 to 2014, with 23 adult patients with a BMI of 48kg/m2, who received a single intragastric air or liquid balloon. We defined efficacy as 10% excess weight loss, and complications, as adverse events consequent to the intragastric balloon diagnosed after the initial accommodative period. We expressed the anthropometric results as means ± standard deviation, comparing the groups with paired T / Student’s T tests, when appropriate, with p<0.05 considered statistically significant. Results: the balloons were effective in 91.3% of the patients, remained in situ for an average of 5.5 months and most of them (65.2%) were air-filled, with a mean excess weight loss of 23.7kg±9.7 (excess weight loss 21.7%±8.9) and mean BMI reduction of 8.3kg/m2±3.3. Complications (17.3%) included abdominal discomfort, balloon deflation and late intolerance, without severe cases. Most of the participants (82.7%) did not experience adverse effects. We removed the intragastric balloons in time, without intercurrences, and 52.2% of these patients underwent bariatric surgery within one month. Conclusion: in our center, intragastric balloons can be successfully used as an initial weight loss procedure, with good tolerance and acceptable complications rates

Elipse, the first procedureless gastric balloon for weight loss: a prospective, observational, open-label, multicenter study

Background and study aims Conventional gastric balloons for weight loss require endoscopy for placement and removal. The Elipse device is swallowed, resides in the stomach for 4 months, and is then expelled. The objectives of this study were to assess the safety of Elipse and to measure its effects on weight loss, metabolic parameters, and quality of life. Methods Each participant swallowed one Elipse device, which was filled with 550mL of filling fluid through a thin delivery catheter that was then removed. Weight was measured every 2 weeks, and metabolic parameters and quality of life were assessed at baseline and at trial exit. Results 34 patients, with a mean body mass index of 34.8 kg/m(2), were enrolled. All 34 patients successfully swallowed the Elipse device. All adverse events were either self-limiting or resolved with medication. All balloons were safely excreted. At 4 months, the mean percent total body weight loss was 10%. Mean waist circumference was reduced by 8.4cm. Improvements were also seen in hemoglobin A1c, triglycerides, low density lipoprotein, and blood pressure. At trial exit, quality of life measures had improved across all domains. Conclusion These results demonstrate clinically significant weight loss with the Elipse, the first procedureless gastric balloon. The weight loss was similar to that seen in previous studies of endoscopically placed balloons. In addition, Elipse therapy led to improvements in waist circumference, several metabolic parameters, and overall quality of lif

Glycerophosphocholine Utilization by Candida albicans

Candida albicans contains four ORFs (GIT1,2,3,4) predicted to encode proteins involved in the transport of glycerophosphodiester metabolites. Previously, we reported that Git1, encoded by ORF 19.34, is responsible for the transport of intact glycerophosphoinositol but not glycerophosphocholine (GroPCho). Here, we report that a strain lacking both GIT3 (ORF 19.1979) and GIT4 (ORF 19.1980) is unable to transport [(3)H]GroPCho into the cell. In the absence of a GroPCho transporter, C. albicans can utilize GroPCho via a mechanism involving extracellular hydrolysis. Upon reintegration of either GIT3 or GIT4 into the genome, measurable uptake of [(3)H]GroPCho is observed. Transport assays and kinetic analyses indicate that Git3 has the greater transport velocity. We present evidence that GDE1 (ORF 19.3936) codes for an enzyme with glycerophosphodiesterase activity against GroPCho. Homozygous deletion of GDE1 results in a buildup of internal GroPCho that is restored to wild type levels by reintegration of GDE1 into the genome. The transcriptional regulator, Pho4, is shown to regulate the expression of GIT3, GIT4, and GDE1. Finally, Git3 is shown to be required for full virulence in a mouse model of disseminated candidiasis, and Git3 sequence orthologs are present in other pathogenic Candida species. In summary, we have characterized multiple aspects of GroPCho utilization by C. albicans and have demonstrated that GroPCho transport plays a key role in the growth of the organism in the host