Chemical-Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.     

Nutrient digestibility and endogenous protein losses in the foregut and small intestine of weaned dairy calves fed calf starters with conventional or enzyme-treated soybean meal

The aims of this experiment were (1) to compare the effects of a soybean meal with an enzymatic treatment (ESBM) to reduce the concentration of antinutritional factors versus a standard soybean meal (SBM) on foregut and small intestine digestion in weaned dairy calves and (2) to estimate the endogenous losses of crude protein (CP) in the small intestine. Our hypothesis was that a diet containing ESBM instead of SBM would improve ruminal and small intestine digestion and absorption of nutrients. A T-cannula was placed in the duodenum, and a second T-cannula was installed in the distal ileum of 12 Holstein calves at approximately 3 wk of age. Calves were weaned on d 42, and on d 50 they were assigned randomly to a quadruplicated 3 × 3 Latin square with 10-d periods. Digesta samples were collected on d 7 and 8 from the ileum and d 9 and 10 from the duodenum. The diets were fed for ad libitum intake and consisted of a calf starter (CS) of 20% CP with SBM as the main source of protein (CTRL), and an isonitrogenous CS with an ESBM instead of SBM (ENZT). A third diet with a low content of CP (10%) and no soy protein was fed to estimate endogenous N losses and digestibilities of test ingredients. Flows and digestibilities of nutrients were compared between CTRL and ENZT and their test ingredients (SBM vs. ESBM, respectively). Duodenal net flows of CP and total AA as well as ruminal microbial protein synthesis per kilogram of digested CP were greater, and flow of nonprotein N and CP true (corrected by endogenous and microbial flows) foregut digestibility were lower with ENZT than CTRL. The apparent small intestine digestibilities of CP and total AA were greater for ESBM than SBM, but there were no differences between the CTRL and ENZT diets. We observed no differences in digestibilities at the duodenum or ileum of starch or NDF, but true small intestine digestibilities of CP and all AA were greater with ENZT than CTRL. Total endogenous protein losses in the small intestine estimated from calves fed the low-CP with no soy protein diet were 37 ± 1.5 g of CP and 29 ± 1.4 g of AA/kg of DMI. These values may be considered the basal endogenous losses as they are similar to values obtained with the regression method, which estimates N losses when dietary N is null. Our results indicated that the inclusion of an ESBM improved the efficiency of ruminal microbial protein synthesis per digested kilogram of organic matter and CP, and increased CP and AA absorption in the small intestine despite a greater proportion of undigested dietary protein entering the duodenum.     

Evidence from sequence information that the interleukin-1 receptor is a transmembrane GTPase

Evidence is presented that the cytoplasmic domain of the type I interleukin-1 receptor (IL-1R) may be a GTPase. This domain conserves segments of hydrophobic amino acids that suggest a structural relatedness to the ras protooncogene protein and other members of the GTPase superfamily, despite a lack of significant detectable sequence homology. When the hydrophobic segments of the IL-1R were aligned with similar segments of the GTPases, it became apparent that the IL-1Rs possess a number of conserved amino acids that represent plausible functional residues for base-specific binding of GTP, magnesium chelation, and phosphate ester hydrolysis. Furthermore, a segment of five contiguous residues were found that is identical between ras and the IL-1R, and which is positioned to form part of the guanine base binding pocket. If this model is correct, then the IL-1Rs possess a highly conserved effector protein binding region, but one that is entirely unrelated to the effector regions of other superfamily members. Therefore, if the IL-1R is indeed a GTPase, then its activation function may be directed to as-yet unrecognized effector target proteins, as part of a unique cellular signal transduction pathway.     

Measurements of single chain form factors by small-angle neutron scattering from polystyrene blends containing high concentrations of labelled molecules

A series of small angle neutron scattering measurements on blends of normal polystyrene (PSH) and labelled (deuterated) polystyrene (PSD) have been made with concentrations of PSD from 5 to 50 mol %. It is shown that the single chain form factor of the polymer in bulk can be obtained from a single concentration measurement for any concentration of labelled molecules, providing the molecular weights of the parent and labelled molecules are the same and the molecular weight distributions are narrow.     

Comparative efficacy of calcipotriol (MC903) cream and betamethasone 17-valerate cream in the treatment of chronic plaque psoriasis. A randomized, double-blind, parallel group multicentre study. Calcipotriol Study Group

PURPOSE: Ultrasound estimated bladder weight was compared before and after surgery for benign prostatic hyperplasia (BPH) to reveal a possible reversible change in bladder hypertrophy. MATERIALS AND METHODS: Ultrasound estimated bladder weight was measured before and after subcapsular (17) or transurethral (16) prostatectomy in 33 male patients with BPH. Sequential changes in the American Urological Association symptom score and urinary flow rate were also examined. RESULTS: Along with a significant improvement in the American Urological Association symptom scores and maximum flow rate, ultrasound estimated bladder weight decreased from 52.9 +/- 22.6 to 31.6 +/- 15.8 gm. in 12 weeks after treatment. In all but 4 patients (29 of 33, or 87.9%) ultrasound estimated bladder weight decreased to less than 35.0 gm. in 12 weeks after treatment. Interestingly, in all patients with an initial ultrasound estimated bladder weight of greater than 80 gm. the bladder weight still remained at an abnormally high level 12 weeks after treatment. CONCLUSIONS: Bladder hypertrophy was completely reversible after the surgical treatment of the obstruction in the majority of patients with BPH. The measurement of ultrasound estimated bladder weight was of value in monitoring therapeutic effects in BPH patients. An extraordinarily high ultrasound estimated bladder weight of 80 gm. or more might suggest degenerative and irreversible pathological changes in the bladder detrusor.     

Glass-ionomer cements in restorative dentistry

This article reviews the current status and future prospects for glass-ionomer materials. These materials are of two chemical types: the older, self-hardening cements, which set by an acid-base neutralization reaction to give relatively brittle materials; and the newer, resin-modified cements, which set partly by polymerization and partly by neutralization. Compared with the self-hardening cements, the latter materials have improved esthetics, improved resistance to moisture, and greater toughness. Both types of glass-ionomer cement bond well to enamel and dentin and release a clinically useful amount of fluoride. They have been used in a variety of applications: as liners or bases, for luting of stainless steel crowns, for Class V restorations in permanent teeth, and for Class II and Class III restorations in primary teeth. The resin-modified glass-ionomers are particularly promising for these latter uses, although it is too early to be sure whether their long-term durability is sufficient. Self-hardening glass-ionomer materials are likely to retain specific niches of clinical application, including in their metal-reinforced and cermet-containing forms.