Rhamnogalacturonan-II cross-linking of plant pectins via boron bridges occurs during polysaccharide synthesis and/or secretion

Rhamnogalacturonan-II (RG-II), a domain of plant cell wall pectins, is able to cross-link with other RG-II domains through borate diester bridges. Although it is known to affect mechanical properties of the cell wall, the biochemical requirements and lifecycle of this cross-linking remain unclear. We developed a PAGE methodology to allow separation of monomeric and dimeric RG-II and used this to study the dynamics of cross-linking in vitro and in vivo. Rosa cells grown in medium with no added boron contained no RG-II dimers, although these re-appeared after addition of boron to the medium. However, other Rosa cultures which were unable to synthesize new polysaccharides did not show dimer formation. We conclude that RG-II normally becomes cross-linked intraprotoplasmically or during secretion, but not post-secretion

Improved glycemic control and vascular function in overweight and obese subjects by glyoxalase 1 inducer formulation

Risk of insulin resistance, impaired glycemic control and cardiovascular disease is excessive in overweight and obese populations. We hypothesised that increasing expression of glyoxalase 1 (Glo1) – an enzyme that catalyses the metabolism of reactive metabolite and glycating agent, methylglyoxal – may improve metabolic and vascular health. Dietary bioactive compounds were screened for Glo1 inducer activity in a functional reporter assay, hits confirmed in cell culture and an optimised Glo1 inducer formulation evaluated in a randomised, placebo-controlled crossover clinical trial in 29 overweight and obese subjects. We found trans-resveratrol (tRES) and hesperetin (HESP), at concentrations achieved clinically, synergised to increase Glo1 expression. In highly overweight subjects (BMI >27.5 kg/m2), tRES-HESP co-formulation increased expression and activity of Glo1 (+ 27%. P<0.05), decreased plasma methylglyoxal (-37%, P<0.05) and total body methylglyoxal-protein glycation (-14%, P<0.01). It decreased fasting and postprandial plasma glucose (-5%, P<0.01 and – 6%, P<0.03, respectively), increased Oral Glucose Insulin Sensitivity index (+42 mlmin-1m-2, P<0.02) and improved arterial dilatation ΔFMD/ΔGTND (95%CI 0.13–2.11). In all subjects, it decreased vascular inflammation marker sICAM-1 (-10%, P<0.01). In previous clinical evaluations, tRES and HESP individually were ineffective. tRES-HESP co-formulation could be a suitable treatment for improved metabolic and vascular health in overweight and obese populations

Anatomy of a cluster IDP. Part 2: Noble gas abundances, trace element geochemistry, isotopic abundances, and trace organic chemistry of several fragments from L2008#5

The topics discussed include the following: noble gas content and release temperatures; trace element abundances; heating summary of cluster fragments; isotopic measurements; and trace organic chemistry

Homoisoflavonoids are potent glucose transporter 2 (GLUT 2) inhibitors–a potential mechanism for the glucose-lowering properties of Polygonatum odoratum

Foods of high carbohydrate content such as sucrose or starch increase postprandial blood glucose concentrations. The glucose absorption system in the intestine comprises two components: sodium-dependent glucose transporter-1 (SGLT1) and glucose transporter 2 (GLUT2). Here five sappanin-type (SAP) homoisoflavonoids were identified as novel potent GLUT2 inhibitors, with three of them isolated from the fibrous roots of Polygonatum odoratum (Mill.) Druce. SAP homoisolflavonoids had a stronger inhibitory effect on 25 mM glucose transport (41.6 ± 2.5, 50.5 ± 7.6, 47.5 ± 1.9, 42.6 ± 2.4, and 45.7 ± 4.1% for EA-1, EA-2, EA-3, MOA, and MOB) than flavonoids (19.3 ± 2.2, 11.5 ± 3.7, 16.4 ± 2.4, 5.3 ± 1.0, 3.7 ± 2.2, and 18.1 ± 2.4% for apigenin, luteolin, quercetin, naringenin, hesperetin, and genistein) and phloretin (28.1 ± 1.6%) at 15 μM. SAP homoisoflavonoids and SGLT1 inhibitors were found to synergistically inhibit the uptake of glucose using an in vitro model comprising Caco-2 cells. This observed new mechanism of the glucose-lowering action of P. odoratum suggests that SAP homoisoflavonoids and their combination with flavonoid monoglucosides show promise as naturally functional ingredients for inclusion in foods and drinks designed to control postprandial glucose levels

Comparative Effectiveness of Drug-Eluting Versus Bare-Metal Stents in Elderly Patients Undergoing Revascularization of Chronic Total Coronary Occlusions Results From the National Cardiovascular Data Registry, 2005–2008

ObjectivesThis study sought to investigate the long-term effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS).BackgroundImproved recanalization techniques have increased interest in percutaneous coronary intervention (PCI) for chronic total coronary occlusion (CTO). The long-term effectiveness of DES and BMS is not known.MethodsWe used data from 10,261 stable patients age ≥65 years at 889 U.S. hospitals who underwent CTO PCI from January 1, 2005, to December 31, 2008, in the NCDR (National Cardiovascular Data Registry) CathPCI Registry with linked Medicare inpatient claims for follow-up. Patient and procedural characteristics, and 30-month death, myocardial infarction, revascularization, and hospitalization for bleeding were evaluated by stent type. Outcomes following stenting were adjusted and compared using propensity score matching.ResultsDES were used for CTO PCI in 8,218 (80%) and BMS in 2,043 (20%). DES patients were younger (74.0 vs. 75.5 years, p < 0.001), had longer lesions (18.8 vs. 16.5 mm, p < 0.001), received more stents (≥2 stents in 45.7% vs. 37.9%, p < 0.001), and underwent multivessel PCI (18.9% vs. 15.1%, p < 0.001). DES implantation was associated with a lower hazard of mortality (hazard ratio [HR]: = 0.72, 95% confidence interval [CI]: 0.60 to 0.86, p < 0.001), a similar hazard for myocardial infarction (HR: 0.85, 95% CI: 0.61 to 1.19, p = 0.35), and subsequent revascularization (HR: 0.94, 95% CI: 0.79 to 1.12, p = 0.48), including PCI (HR: 0.98, 95% CI: 0.83 to 1.19, p = 0.87) and coronary artery bypass grafting (HR: 0.71, 95% CI: 0.46 to 1.10, p = 0.12). Hospitalization for bleeding was also similar for DES versus BMS (HR: 0.92; 95% CI: 0.61 to 1.39, p = 0.70).ConclusionsCompared with BMS, DES use in stable patients undergoing CTO PCI was associated with lower mortality, as well as similar myocardial infarction and repeat revascularization rates without an increase in subsequent bleeding requiring hospitalization

Percutaneous Coronary Intervention and Drug-Eluting Stent Use Among Patients ≥85 Years of Age in the United States

ObjectivesThis study assessed the comparative effectiveness of drug-eluting stents (DES) versus bare-metal stents (BMS) among patients ≥85 years of age.BackgroundDespite an aging population, little is known about the comparative effectiveness of DES versus BMS among patients age ≥85 years undergoing percutaneous coronary intervention (PCI).MethodsWe examined 471,006 PCI patients age ≥65 years at 947 hospitals in the National Cardiovascular Data Registry between 2004 and 2008 and linked to Medicare claims data. Long-term outcomes (median follow-up 640.8 ± 423.5 days) were compared between users of DES and BMS.ResultsPatients age ≥85 years comprise an increasing proportion of PCIs performed among elderly subjects, yet rates of DES use declined the most in this age group. Compared with BMS, use of DES was associated with lower mortality: age ≥85 years, 29% versus 38% (adjusted hazard ratio [HR]: 0.80 [95% confidence interval (CI): 0.77 to 0.83]); age 75 to 84 years, 17% versus 25% (HR: 0.77 [95% CI: 0.75 to 0.79]); and age 65 to 74 years, 10% versus 16% (HR: 0.73 [95% CI: 0.71 to 0.75]). However, the adjusted mortality difference narrowed with increasing age (pinteraction <0.001). In contrast, the adjusted HR for myocardial infarction rehospitalization associated with DES use was significantly lower with increasing age: age ≥85 years, 9% versus 12% (HR: 0.77 [95% CI: 0.71 to 0.83]); age 75 to 84 years, 7% versus 9% (HR: 0.81 [95% CI: 0.77 to 0.84]); and age 65 to 74 years, 7% versus 8% (HR: 0.84 [95% CI: 0.80 to 0.88]) (pinteraction <0.001).ConclusionsIn this national study of older patients undergoing PCI, declines in DES use were most pronounced among those aged ≥85 years, yet lower adverse-event rates associated with DES versus BMS use were observed

Development of peptide-based lineage-specific serology for chronic Chagas disease: geographical and clinical distribution of epitope recognition.

BACKGROUND: Chagas disease, caused by infection with the protozoan Trypanosoma cruzi, remains a serious public health issue in Latin America. Genetically diverse, the species is sub-divided into six lineages, known as TcI-TcVI, which have disparate geographical and ecological distributions. TcII, TcV, and TcVI are associated with severe human disease in the Southern Cone countries, whereas TcI is associated with cardiomyopathy north of the Amazon. T. cruzi persists as a chronic infection, with cardiac and/or gastrointestinal symptoms developing years or decades after initial infection. Identifying an individual's history of T. cruzi lineage infection directly by genotyping of the parasite is complicated by the low parasitaemia and sequestration in the host tissues. METHODOLOGY/PRINCIPAL FINDINGS: We have applied here serology against lineage-specific epitopes of the T. cruzi surface antigen TSSA, as an indirect approach to allow identification of infecting lineage. Chagasic sera from chronic patients from a range of endemic countries were tested by ELISA against synthetic peptides representing lineage-specific TSSA epitopes bound to avidin-coated ELISA plates via a biotin labelled polyethylene glycol-glycine spacer to increase rotation and ensure each amino acid side chain could freely interact with their antibodies. 79/113 (70%) of samples from Brazil, Bolivia, and Argentina recognised the TSSA epitope common to lineages TcII/TcV/TcVI. Comparison with clinical information showed that a higher proportion of Brazilian TSSApep-II/V/VI responders had ECG abnormalities than non-responders (38% vs 17%; p<0.0001). Among northern chagasic sera 4/20 (20%) from Ecuador reacted with this peptide; 1/12 Venezuelan and 1/34 Colombian samples reacted with TSSApep-IV. In addition, a proposed TcI-specific epitope, described elsewhere, was demonstrated here to be highly conserved across lineages and therefore not applicable to lineage-specific serology. CONCLUSIONS/SIGNIFICANCE: These results demonstrate the considerable potential for synthetic peptide serology to investigate the infection history of individuals, geographical and clinical associations of T. cruzi lineages

Accessing bacterial dark matter for improved enzyme discovery and engineering

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