Sugar-induced molten-globule model

Proteins denature at low pH because of intramolecular electrostatic repulsions. The addition of salt partially overcomes this repulsion for some proteins, yielding a collapsed conformation called the A-state. A-states have characteristics expected for the molten globule, a notional kinetic protein folding intermediate. Here we show that the addition of neutral sugars to solutions of acid-denatured equine ferricytochrome c induces formation of the A-state in the absence of added salt. We characterized the structure and stability of the sugar-induced A-state with circular dichroism spectropolarimetry (CD) and NMR-monitored hydrogen-deuterium exchange experiments. We also examined the stability of the sugar-induced A-state as a function of sugar size and concentration. The results are interpreted using several models and we conclude that the stabilizing effect is consistent with increased steric repulsion between the protein and the sugar solutions.     

Respiratory syncytial virus (RSV) disease and prospects for its control

Respiratory syncytial virus (RSV) is a major virus pathogen of infants and young children, an important cause of disease in adults and is responsible for a significant amount of excess morbidity and mortality in the elderly. It also can be devastating in immunosuppressed populations. Vaccines are being developed, but none are currently licensed. Moreover, even if one or more are approved, they may not be suitable for some populations vulnerable to RSV (e.g. very young infants and the immunosuppressed). Ribavirin and immunoglobulin preparations with high titers of RSV-specific neutralizing antibodies are currently approved for use to treat and prevent RSV infection. However, neither of these is cost-effective or simple to administer. New agents are needed to reduce the impact of RSV. This review is concerned with the means currently available for controlling RSV, the search for new agents effective against this virus, and future prospects for preventing and treating RSV infections.     

Uterine relaxation responses to calcitonin gene-related peptide and calcitonin gene-related peptide receptors decreased during labor in rats

OBJECTIVES: Our purpose was to investigate (1) whether uterine relaxation responses to calcitonin gene-related peptide are differentially regulated during pregnancy and labor, (2) the involvement of nitric oxide in smooth muscle relaxant action of calcitonin gene-related peptide in the rat uterus, (3) whether receptors for calcitonin gene-related peptide are expressed in rat uterus, and if so (4) whether the concentrations of these receptors are differently regulated during pregnancy and labor. STUDY DESIGN: Rats were killed on day 18 of gestation, at the time of spontaneous labor, or postpartum day 2. The uteri were removed for in vitro contractility measurements, nitric oxide production, and calcitonin gene-related peptide receptor binding assay. RESULTS: (1) Calcitonin gene-related peptide induced a dose-dependent relaxation in spontaneously contracting uterine strips from pregnant rats on day 18 of gestation; (2) the relaxation effects of calcitonin gene-related peptide on the uterus were decreased during spontaneous delivery at term and post partum compared with that during pregnancy; (3) calcitonin gene-related peptide-induced relaxation was inhibited by pretreatment of the uterine tissue with a calcitonin gene-related peptide receptor antagonist, calcitonin gene-related peptide(8-37); (4) nitric oxide synthesis inhibitor (N(G)-nitro-L-arginine methyl ester) and soluble guanylate cyclase inhibitor (LY83583) significantly decreased calcitonin gene-related peptide-induced relaxation of the rat uterus during pregnancy; (5) calcitonin gene-related peptide increased the uterine nitric oxide production in pregnant rats, and this increase was obliterated in the presence of calcitonin gene-related peptide(8-37); and (6) calcitonin gene-related peptide receptors are present in rat uterus, and the concentration of these receptors dramatically increases during pregnancy and decreases during labor at term. CONCLUSIONS: Calcitonin gene-related peptide inhibits uterine spontaneous contractions in rats during pregnancy but not during labor and post partum. The inhibitory effects of calcitonin gene-related peptide on uterine contractility appear to be modulated, at least in part, by the activation of nitric oxide generation in the rat uterus. Changes in calcitonin gene-related peptide receptors could contribute to the changes in calcitonin gene-related peptide-mediated uterine relaxation during pregnancy and labor.     

Trends in mortality of childhood-onset insulin-dependent diabetes mellitus in Leicestershire: 1940-1991

The relative risk of death by calendar date of diagnosis was investigated in a population-based incident cohort of 845 (463 males:382 females) IDDM diagnosed in Leicestershire before the age of 17 years between 1940 and 1989. The mortality status of 844 (99.9%) patients was determined as of the 31 December 1991, representing 14,346 person-years of risk. Trends in relative risk of death were investigated using Cox proportional hazards modelling for within cohort comparisons and age/sex and calendar time adjusted standardized mortality ratios (SMR) using generalized linear modelling for external comparisons. Median age at diagnosis was 10 years (range 3 months to 16 years); median duration of diabetes 15 years (range 1-51 years). Forty-four patients had died (5.2%; median age at death 31 years, range 11-51 years). A further four patients died at presentation (within 24 h) from ketoacidosis and are excluded from all analyses. Calendar date of diagnosis was found to be an important predictor of mortality. Adjusting for attained age there was evidence of a decline in relative risk of death with calendar date of diagnosis of 3.4% (95% CI, 0.005-6.9%) per annum, equivalent to a 32% fall per decade (95% CI, 5-51%), or 84% (95% CI, 21-97) from 1940 to 1989. The data are consistent with a large fall in mortality between the 1940s and 1950s representing over 50% of the total reduction in mortality between 1940 and 1991. Neither sex nor age at diagnosis were significant predictors of mortality. Over the study period 1940-89 the SMR (male and female combined) fell from 981 (541-1556) to 238 (60-953) relative to the general population. This population-based study shows that the prognosis for Type 1 (insulin-dependent) diabetes mellitus has improved markedly over the period 1940-1991.     

Growth kinetics and treatment response of the intracerebral rat 9L brain tumor model: a quantitative in vivo study using magnetic resonance imaging

We report the use of magnetic resonance imaging (MRI) for in situ tumor growth rate studies of experimental intracranial 9L tumors. T2-weighted spin-echo coronal magnetic resonance images of rat brains with 9L tumors were obtained every 2 days beginning at 8-11 days postimplantation using a 7 tesla MRI system. Tumors were clearly delineated in the images as a hyperintense region with a relatively well-demarcated border and minimal peritumoral edema. Tumor volumes from individual slices were summed together to yield the total tumor volume. The accuracy of this methodology for volumetric determination was verified by MRI phantom studies. Tumor growth rates determined from sequential MRI measurements of tumor volumes were quantitated in terms of volumetric doubling time. Tumor doubling times were found to range from 50 to 81 h, with an average of 66 +/- 8 h (n = 10). Intracranial 9L tumors were found to grow exponentially over the entire life span of the animal, allowing treated animals to serve as their own controls since the volumetric doubling time could be determined from three to four MRI scans before treatment administration. The intracerebral tumor growth delay following a single injection of 1, 3-bis(2-chloroethyl)-1-nitrosourea (13.3 mg/kg i.p.) allowed for noninvasive determination of in vivo log cell kill. A 2.0 +/- 0.2 (n = 3) log cell kill from 1,3-bis(2-chloroethyl)-1-nitrosourea treatment was found from post-treatment MRI volume measurements. These results demonstrate that MRI provides a powerful and sensitive method for assessing the growth and treatment response of intracranial 9L tumors in the rat.     

Sesquiterpenoids of the drimane class from a sponge of the genus Dysidea

Ten sesquiterpenoids, including seven new ones, have been isolated from an undescribed sponge of the genus Dysidea. Compounds 1-8 are sesquiterpenoids of the drimane class, while 9 and 10 are 12-norsesquiterpenoids of the same structural class. The structures of novel compounds have been determined by combined spectroscopic methods. These compounds exhibited moderate antimicrobial and enzyme inhibitory (Na+/K(+)-ATPase and PLA2) activities.     

Electrooxidation of CO and CO/H2 mixtures on a Pt-Sn catalyst prepared by an implantation method

A new type of ion implantation technique is used to create a non-equilibrium Pt-Sn(IMP) near-surface alloy with ca. 8.6 at% Sn. The surface composition was determined by low-energy ion-scattering (LEIS). The kinetics of the electrooxidation of CO and 2% CO/H₂ mixtures on Pt-Sn(IMP) is essentially identical to that of Pt₃Sn(110). The fact that any non-equilibrium composition can be easily prepared by this implantation method opens an interesting practical opportunity to create a new Pt-Sn alloy fuel cell catalyst having an otherwise unobtainable surface composition of Sn. This method also appears to have general utility in alloy catalysis as a means of exploring compositions in thermodynamically unfavorable regions of the bulk phase diagram. This revised version was published online in July 2006 with corrections to the Cover Date.     

A kinetic and surface study of the thermal decomposition of cellulose powder in inert and oxidizing atmospheres

The thermal decomposition of fibrous cellulose powder from 275° to 340°C has been studied by thermogravimetry, scanning electron microscopy, krypton adsorption, and gas-chromatographic analysis of the gaseous products arising from pyrolysis in various oxidizing and inert atmospheres. The reaction kinetics fit a phase boundary model where the rate is controlled by the movement of an interface through a cylindrical particle and the principal kinetic parameters fit a compensation curve described previously for the decomposition of wood products. An explanation of the physical mechanism of pyrolysis is proposed which is consistent with the observed rate data and the structural changes observed by scanning electron microscopy.     

Reactive Laser Ablation Synthesis of Nanosize Alumina Powder

An aluminum (Al) target was laser ablated in an oxygen (O₂) atmosphere, producing nanosize alumina (Al₂O₃) powder. The powder surface area decreased (and the particle size increased) with both increasing oxygen pressure and laser fluence. All powders produced had surface areas between 135 and 250 m²/g, corresponding to primary particle sizes ranging from 7 to 3 nm in radius. Phase evolution with temperature was studied via X-ray diffraction. These powders showed a direct transformation from γ- to α-alumina at approximately 1200°C, bypassing other transition alumina phases, while still maintaining small particle size ( 30 nm). Despite the nanosize particles, green densities equal to 54% of the skeletal density (i.e., true density of the solid phase) were obtained by uniaxial pressing at 40 MPa.