Phycobiliproteins (PBPs) are a group of brilliant pigment proteins found in cyanobacteria and red algae; their synthesis and accumulation depend on several factors such as the type of strain ...employed, nutrient concentration, light intensity, light regimes, and others. This study evaluates the effect of macronutrients (citrate buffer, NaNO3, K2HPO4, MgSO4, CaCl2, Na2CO3, and EDTA) and the concentration of trace metals in BG-11 media on the accumulation of PBPs in a thermotolerant strain of Oscillatoria sp. The strain was grown in BG-11 media at 28 °C with a light:dark cycle of 12:12 h at 100 μmol m–2 s–1 for 15 days, and the effect of nutrients was evaluated using a Plackett–Burman Design followed by optimization using a response surface methodology. Results from the concentration of trace metals show that it can be reduced up to half-strength in its initial concentration without affecting both biomass and PBPs. Results from the Plackett–Burman Design revealed that only NaNO3, Na2CO3, and K2HPO4 show a significant increase in PBP production. Optimization employed a central Non-Factorial Response Surface Design with three levels and four factors (34) using NaNO3, Na2CO3, K2HPO4, and trace metals as variables, while the other components of BG-11 media (citrate buffer, MgSO4, CaCl2, and EDTA) were used in half of their initial concentration. Results from the optimization show that interaction between Na2CO3 and K2HPO4 highly increased PBPs’ concentration, with values of 15.21, 3.95, and 1.89 (% w/w), respectively. These results demonstrate that identifying and adjusting the concentration of critical nutrients can increase the concentration of PBPs up to two times for phycocyanin and allophycocyanin while four times for phycoerythrin. Finally, the reduction in non-key nutrients’ concentration will reduce the production costs of colorants at an industrial scale and increase the sustainability of the process.
Currently, molecular diagnosis of haemophilia A and B (HA and HB) highlights the excess risk-inhibitor development associated with specific mutations, and enables carrier testing of female relatives ...and prenatal or preimplantation genetic diagnosis. Molecular testing for HA also helps distinguish it from von Willebrand disease (VWD). Next-generation sequencing (NGS) allows simultaneous investigation of several complete genes, even though they may span very extensive regions. This study aimed to evaluate the usefulness of a molecular algorithm employing an NGS approach for sequencing the complete F8, F9 and VWF genes. The proposed algorithm includes the detection of inversions of introns 1 and 22, an NGS custom panel (the entire F8, F9 and VWF genes), and multiplex ligation-dependent probe amplification (MLPA) analysis. A total of 102 samples (97 FVIII- and FIX-deficient patients, and five female carriers) were studied. IVS-22 screening identified 11 out of 20 severe HA patients and one female carrier. IVS-1 analysis did not reveal any alterations. The NGS approach gave positive results in 88 cases, allowing the differential diagnosis of mild/moderate HA and VWD in eight cases. MLPA confirmed one large exon deletion. Only one case did have no pathogenic variants. The proposed algorithm had an overall success rate of 99 %. In conclusion, our evaluation demonstrates that this algorithm can reliably identify pathogenic variants and diagnose patients with HA, HB or VWD.
Epigenomic mechanisms regulate distinct aspects of the inflammatory response in immune cells. Despite the central role for microglia in neuroinflammation and neurodegeneration, little is known about ...their epigenomic regulation of the inflammatory response. Here, we show that Ten-eleven translocation 2 (TET2) methylcytosine dioxygenase expression is increased in microglia upon stimulation with various inflammogens through a NF-κB-dependent pathway. We found that TET2 regulates early gene transcriptional changes, leading to early metabolic alterations, as well as a later inflammatory response independently of its enzymatic activity. We further show that TET2 regulates the proinflammatory response in microglia of mice intraperitoneally injected with LPS. We observed that microglia associated with amyloid β plaques expressed TET2 in brain tissue from individuals with Alzheimer’s disease (AD) and in 5xFAD mice. Collectively, our findings show that TET2 plays an important role in the microglial inflammatory response and suggest TET2 as a potential target to combat neurodegenerative brain disorders.
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•TET2 is upregulated in microglia cells upon various inflammatory stimuli•TET2 regulates TLR-4-induced type I IFN response and LPS-induced aerobic glycolysis•TET2 regulates the proinflammatory response induced by LPS in vitro and in vivo•TET2 is expressed by amyloid β plaque-associated microglia in AD brains
Microglia play a key role in neuroinflammation and neurodegeneration in different neurodegenerative diseases, but little is known about the epigenetic modifying enzymes regulating their inflammatory response. Carrillo-Jimenez et al. identify TET2 as a major regulator of the microglia proinflammatory response and suggest that, by targeting this protein, microglial activation could be impaired.
Since 2004, malaria transmission on Bioko Island has declined significantly as a result of the scaling-up of control interventions. The aim of eliminating malaria from the Island remains elusive, ...however, underscoring the need to adapt control to the local context. Understanding the factors driving the risk of malaria infection is critical to inform optimal suits of interventions in this adaptive approach.
This study used individual and household-level data from the 2015 and 2018 annual malaria indicator surveys on Bioko Island, as well as remotely-sensed environmental data in multilevel logistic regression models to quantify the odds of malaria infection. The analyses were stratified by urban and rural settings and by survey year.
Malaria prevalence was higher in 10-14-year-old children and similar between female and male individuals. After adjusting for demographic factors and other covariates, many of the variables investigated showed no significant association with malaria infection. The factor most strongly associated was history of travel to mainland Equatorial Guinea (mEG), which increased the odds significantly both in urban and rural settings (people who travelled had 4 times the odds of infection). Sleeping under a long-lasting insecticidal net decreased significantly the odds of malaria across urban and rural settings and survey years (net users had around 30% less odds of infection), highlighting their contribution to malaria control on the Island. Improved housing conditions indicated some protection, though this was not consistent across settings and survey year.
Malaria risk on Bioko Island is heterogeneous and determined by a combination of factors interacting with local mosquito ecology. These interactions grant further investigation in order to better adapt control according to need. The single most important risk factor identified was travel to mEG, in line with previous investigations, and represents a great challenge for the success of malaria control on the Island.
High-resolution Fourier transform infrared (FTIR) solar observations are particularly relevant for climate studies, as they allow atmospheric gaseous composition and multiple climate processes to be ...monitored in detail. In this context, the present paper provides an overview of 20 years of FTIR measurements taken in the framework of the NDACC (Network for the Detection of Atmospheric Composition Change) from 1999 to 2018 at the subtropical Izaña Observatory (IZO, Spain). Firstly, long-term instrumental performance is comprehensively assessed, corroborating the temporal stability and reliable instrumental characterization of the two FTIR spectrometers installed at IZO since 1999. Then, the time series of all trace gases contributing to NDACC at IZO are presented (i.e. C2H6, CH4, ClONO2, CO, HCl, HCN, H2CO, HF, HNO3, N2O, NO2, NO, O3, carbonyl sulfide (OCS), and water vapour isotopologues H216O, H218O, and HD16O), reviewing the major accomplishments drawn from these observations. In order to examine the quality and long-term consistency of the IZO FTIR observations, a comparison of those NDACC products for which other high-quality measurement techniques are available at IZO has been performed (i.e. CH4, CO, H2O, NO2, N2O, and O3). This quality assessment was carried out on different timescales to examine what temporal signals are captured by the FTIR records, and to what extent. After 20 years of operation, the IZO NDACC FTIR observations have been found to be very consistent and reliable over time, demonstrating great potential for climate research. Long-term NDACC FTIR data sets, such as IZO, are indispensable tools for the investigation of atmospheric composition trends, multi-year phenomena, and complex climate feedback processes, as well as for the validation of past and present space-based missions and chemistry climate models.
Weight loss of 5% to 10% can improve type 2 diabetes and related comorbidities. Few safe, effective weight-management drugs are currently available.
To investigate efficacy and safety of liraglutide ...vs placebo for weight management in adults with overweight or obesity and type 2 diabetes.
Fifty-six-week randomized (2:1:1), double-blind, placebo-controlled, parallel-group trial with 12-week observational off-drug follow-up period. The study was conducted at 126 sites in 9 countries between June 2011 and January 2013. Of 1361 participants assessed for eligibility, 846 were randomized. Inclusion criteria were body mass index of 27.0 or greater, age 18 years or older, taking 0 to 3 oral hypoglycemic agents (metformin, thiazolidinedione, sulfonylurea) with stable body weight, and glycated hemoglobin level 7.0% to 10.0%.
Once-daily, subcutaneous liraglutide (3.0 mg) (n = 423), liraglutide (1.8 mg) (n = 211), or placebo (n = 212), all as adjunct to 500 kcal/d dietary deficit and increased physical activity (≥150 min/wk).
Three coprimary end points: relative change in weight, proportion of participants losing 5% or more, or more than 10%, of baseline weight at week 56.
Baseline weight was 105.7 kg with liraglutide (3.0-mg dose), 105.8 kg with liraglutide (1.8-mg dose), and 106.5 kg with placebo. Weight loss was 6.0% (6.4 kg) with liraglutide (3.0-mg dose), 4.7% (5.0 kg) with liraglutide (1.8-mg dose), and 2.0% (2.2 kg) with placebo (estimated difference for liraglutide 3.0 mg vs placebo, -4.00% 95% CI, -5.10% to -2.90%; liraglutide 1.8 mg vs placebo, -2.71% 95% CI, -4.00% to -1.42%; P < .001 for both). Weight loss of 5% or greater occurred in 54.3% with liraglutide (3.0 mg) and 40.4% with liraglutide (1.8 mg) vs 21.4% with placebo (estimated difference for liraglutide 3.0 mg vs placebo, 32.9% 95% CI, 24.6% to 41.2%; for liraglutide 1.8 mg vs placebo, 19.0% 95% CI, 9.1% to 28.8%; P < .001 for both). Weight loss greater than 10% occurred in 25.2% with liraglutide (3.0 mg) and 15.9% with liraglutide (1.8 mg) vs 6.7% with placebo (estimated difference for liraglutide 3.0 mg vs placebo, 18.5% 95% CI, 12.7% to 24.4%, P < .001; for liraglutide 1.8 mg vs placebo, 9.3% 95% CI, 2.7% to 15.8%, P = .006). More gastrointestinal disorders were reported with liraglutide (3.0 mg) vs liraglutide (1.8 mg) and placebo. No pancreatitis was reported.
Among overweight and obese participants with type 2 diabetes, use of subcutaneous liraglutide (3.0 mg) daily, compared with placebo, resulted in weight loss over 56 weeks. Further studies are needed to evaluate longer-term efficacy and safety.
clinicaltrials.gov Identifier:NCT01272232.
Agave lechuguilla Torr., of the family Agavaceae, is distributed from southwestern United States to southern Mexico and is one of the most representative species of arid and semiarid regions. Its ...fiber is extracted for multiple purposes. The objective of this study was to generate a robust model to predict dry fiber yield (Dfw) rapidly, simply, and inexpensively. We used a power model in its linear form and bioclimatic areas as dummy variables. Training, generation (80%) and validation (20%) of the model was performed using machine learning with the package 'caret' of R. Using canonical correlation analysis (CCA), we evaluated the relationship of Dwf to bioclimatic variables. The principal components analysis (PCA) generated two bioclimatic zones, each with different A. lechuguilla productivities. We evaluated 499 individuals in four states of Mexico. The crown diameter (Cd) of this species adequately predicts its fiber dry weight (R.sup.2 = 0.6327; p < 0.05). The intercept (beta.sub.0 ), slope lnCd (beta.sub.1 ), zone (beta.sub.2 ) and interaction lnCd:Zona (beta.sub.3 ) of the dummy model was statistically significant (p < 0.05), giving origin to an equation for each bioclimatic zone. The CCA indicates a positive correlation between minimum temperature of the coldest month (Bio 6) and Dwf (r = 0.84 and p < 0.05). In conclusion, because of the decrease in Bio 6 of more than 0.5°C by 2050, the species could be vulnerable to climate change, and A. lechuguilla fiber production could be affected gradually in the coming years.
We examined trends, characteristics and in-hospital outcomes in mechanical and bioprosthetic surgical mitral valve replacement (SMVR) among patients with and without chronic obstructive pulmonary ...disease (COPD) in Spain from 2001 to 2015. We also identified factors associated with in-hospital mortality (IHM) in both groups of patients according to the implanted valve type.
We analyzed data from the Spanish National Hospital Discharge Database for patients aged 40 years or over. We selected admissions of patients whose medical procedures included SMVR. We grouped hospitalizations by COPD status.
Over 43,024 patients identified, 83.63% underwent mechanical mitral valve replacement and 16.37% bioprosthetic valve (6.71% and 7.78% with COPD, respectively). The incidence of SMVR decreased for mechanical valves and increased for bioprosthetic valves over time in both groups of patients. The incidence of SMVR admissions was lower among COPD patients than in those without COPD, both for mechanical and bioprosthetic valves. IHM decreased significantly over time, regardless of the type of valve, in both groups of patients. COPD was associated with a significant increase in IHM, but only among patients who underwent bioprosthetic SMVR (OR 1.32, 95% CI 1.01-1.73).
The incidence of mechanical SMVR decreased while that of bioprosthetic SMVR increased over time in both groups of patients. COPD patients were less surgically operated than non-COPD patients for both valve types. In COPD patients, bioprosthetic SMVR was proportionally more used than mechanical SMVR. Mortality decreased over time for both valve types in patients with and without COPD. COPD increased in-hospital mortality among patients undergoing a biological SMVR.
During red wine maturation in contact with oak wood, C-glucosidic ellagitannins can react with anthocyanins, leading to new pigments. In this work the thermodynamic and kinetic constants of the ...network pH-dependent equilibrium of a new myrtillin (delphinidin 3-O-glucoside)–vescalagin hybrid pigment (1-deoxyvescalagin-(1β→8)-myrtillin) have been determined by UV–visible absorption and stopped-flow experiments and compared to those determined for myrtillin. The vescalagin substitution at the C-8′ center of myrtillin entails important variations in the pigment behavior upon pH changes. The hybrid pigment showed lower pK′a and pK a values and a much higher value of K t. As a consequence, at moderately acidic pH values (4 < pH < 6), the percentage of the hemiketal is much lower and the quinoidal base and the (E)-chalcone represent higher percentages relative to those for myrtillin. Therefore, the hybrid pigment can provide in slightly acidic or neutral solutions an exceptionally different color compared to that of myrtillin.
Abstract Background We report the case of a 34-year-old man who underwent Kasai portoenterostomy for biliary atresia at 6 weeks of age. In 2011, pulmonary hypertension was diagnosed and he began ...treatment with sildenafil. In 2012, he presented with an episode of upper gastrointestinal bleeding secondary to esophageal varices resistant to treatment. Later, he exhibited liver dysfunction. He was included on the waiting list for transplantation on May 29, 2013, with a Model for End-stage Liver Disease score of 24. Methods He underwent liver transplantation with an isogroup graft from a brain dead donor on June 9, 2013. Native hepatectomy was laborious owing to important collateral circulation and adhesions after previous operations, which had injured loops of the small bowel (SB). Orthotopic implantation was accomplished with direct anastomosis of the upper liver cava vein to the right atrium of the receiver. Portal and arterial anastomoses were performed as usual. Biliary reconstruction surgery by hepatojejunostomy was delayed 24 hours owing to SB loops injuries. Results Graft viability was confirmed by normal hepatic function. Postoperative complications included abdominal compartment syndrome treated by decompressing laparotomy, severe pulmonary alveolar hemorrhage resolved with artery embolization and endotracheal intubation, intraabdominal abscess requiring percutaneous drain, and stroke requiring long-term rehabilitation. He is currently asymptomatic, presents normal graft function, and receives sildenafil because of pulmonary hypertension. Conclusions The association of situs inversus and biliary atresia is low. There is no consensus on the optimal operative approach to liver transplantation. An individualized assessment and multidisciplinary patient management are required.
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