Characterisation of the Dynamic Interactions between Complex N-Glycans and Human CD22

CD22 (Siglec-2) is a B-cell surface inhibitory protein capable of selectively recognising sialylated glycans, thus dampening autoimmune responses against self-antigens. Here we have characterised the dynamic recognition of complex-type N-glycans by human CD22 by means of orthogonal approaches including NMR spectroscopy, computational methods and biophysical assays. We provide new molecular insights into the binding mode of sialoglycans in complex with h-CD22, highlighting the role of the sialic acid galactose moieties in the recognition process, elucidating the conformational behaviour of complex-type N-glycans bound to Siglec-2 and dissecting the formation of CD22 homo-oligomers on the B-cell surface. Our results could enable the development of additional therapeutics capable of modulating the activity of h-CD22 in autoimmune diseases and malignancies derived from B-cells.     

Utilisation of fruit fibres in conventional and reduced‐fat cooked‐meat sausages

The effect of several fruit dietary fibres on the sensory properties of conventional and reduced‐fat cooked‐meat sausages is studied. Fruit fibres were assayed at 15 and 30 g kg^?1 concentrations. The energy value reduction of the final products was close to 30%. Instrumental measurements of colour and texture were performed. Sensory properties were estimated by hedonic tests. A correlation principal component analysis was performed. The results of textural analysis showed that the differences between batches were mainly related to the fat content. However, sensory analysis indicated that the most appreciated batches were those manufactured with orange fibre, although their colour was more yellow than the remainder. As a consequence, it is possible to manufacture conventional and hypocaloric cooked sausages containing fruit fibres mainly at a concentration of 15 g kg^?1 of fibre and obtain a sensorial acceptable product. Copyright © 2006 Society of Chemical Industry     

Optimal Stopping for I.I.D. Random Variables Based on the Sequential Information of the Location of Relative Records Only

Abstract

Let X _j , j = 1,…, n be independent and identically distributed random variables. Like in the classical secretary problem, the optimal stopper only observes Y _j  = 1, if X _j is a (relative) record, and Y _j  = 0, otherwise. The actual X _j values are not revealed. The goal is to maximize the expected X value at which one stops. We show that the optimal number of observations one should skip before considering stopping depends heavily on the underlying distribution.     

The Impact of Nonalcoholic Fatty Liver Disease on Renal Function in Children with Overweight/Obesity

The association between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease has attracted interest and attention over recent years. However, no data are available in children. We determined whether children with NAFLD show signs of renal functional alterations, as determined by estimated glomerular filtration rate (eGFR) and urinary albumin excretion. We studied 596 children with overweight/obesity, 268 with NAFLD (hepatic fat fraction ≥5% on magnetic resonance imaging) and 328 without NAFLD, and 130 healthy normal-weight controls. Decreased GFR was defined as eGFR < 90 mL/min/1.73 m². Abnormal albuminuria was defined as urinary excretion of ≥30 mg/24 h of albumin. A greater prevalence of eGFR < 90 mL/min/1.73 m² was observed in patients with NAFLD compared to those without liver involvement and healthy subjects (17.5% vs. 6.7% vs. 0.77%; p < 0.0001). The proportion of children with abnormal albuminuria was also higher in the NAFLD group compared to those without NAFLD, and controls (9.3% vs. 4.0% vs. 0; p < 0.0001). Multivariate logistic regression analysis revealed that NAFLD was associated with decreased eGFR and/or microalbuminuria (odds ratio, 2.54 (confidence interval, 1.16–5.57); p < 0.05) independently of anthropometric and clinical variables. Children with NAFLD are at risk for early renal dysfunction. Recognition of this abnormality in the young may help to prevent the ongoing development of the disease.     

Bimodal polypropylene through binary metallocene catalytic systems: comparison between hybrid and mixed heterogeneous catalysts

Polypropylene with wider or bimodal molecular weight distribution is required for numerous applications since low molecular weight chains improve processability and high molecular weight fraction is required to get good mechanical properties. There are several routes to achieve a bimodal resin but the use of a binary catalytic system seems to be the most attractive, particularly with metallocenes combination. From a previous work two metallocenes were selected because they lead to polypropylenes with average molecular weights that differ in one order of magnitude. Two types of binary systems have been investigated, hybrid catalysts (two metallocenes loaded on the same support) and physical mixtures (two independent supported metallocenes that are introduced to the reactor and start the polymerization together), using different ratios, i.e., 25–75, 50–50, 75–25, at three reaction temperatures, i.e., 30, 50 and 70 °C. Most of the binary catalytic systems lead to bimodal molecular weight distributions. Polypropylenes produced by mixed catalysts are greatly influenced by the most active catalyst, while in PP coming from hybrid catalysts, as there is a strong interaction between both metallocenes, each one contributes according to its presence in the hybrid catalyst. Therefore, properties of obtained bimodal polypropylenes are quite influenced by the ratio between both metallocenes.     

Dual‐Action Cancer Therapy with Targeted Porous Silicon Nanovectors

There is a pressing need to develop more effective therapeutics to fight cancer. An idyllic chemotherapeutic is expected to overcome drug resistance of tumors and minimize harmful side effects to healthy tissues. Antibody‐functionalized porous silicon nanoparticles loaded with a combination of chemotherapy drug and gold nanoclusters (AuNCs) are developed. These nanocarriers are observed to selectively deliver both payloads, the chemotherapy drug and AuNCs, to human B cells. The accumulation of AuNCs to target cells and subsequent exposure to an external electromagnetic field in the microwave region render them more susceptible to the codelivered drug. This approach represents a targeted two‐stage delivery nanocarrier that benefits from a dual therapeutic action that results in enhanced cytotoxicity.     

Influence of the dispersion of Nanoclays on the cellular structure of foams based on polystyrene

In the present work blends of polystyrene (PS) with sepiolites have been produced using a melt extrusion process. The dispersion degree of the sepiolites in the PS has been analyzed by dynamic shear rheology and X-ray micro-computed tomography. Sepiolites treated with quaternary ammonium salts (O-QASEP) are better dispersed in the PS matrix than natural sepiolites (N-SEP) or sepiolites organo-modified with silane groups (O-SGSEP). A percolated network is obtained when using 6.0 wt% of O-QASEP, 8.0 wt% of N-SEP and 10.0 wt% of O-SGSEP. It has been shown that multiple extrusion processes have a negative effect on the polymer architecture. They produce a reduction in the length of the polymeric chains, and they do not lead to a better dispersion of the particles in the polymer matrix. Foams have been produced using a gas dissolution foaming process, where a strong effect of the dispersion degree on the cellular structure of the different foams was found. The effects on the cellular structure obtained by using different types of sepiolites, different contents of sepiolites and different extrusion conditions have been analyzed. The foams produced with the formulations containing O-QASEP present the lowest cell size and the most homogeneous cellular structures.