Conformations and folding of lysozyme ions in vacuo

Proton transfer reactivity of isolated charge states of the protein hen egg-white lysozyme shows that multiple distinct conformations of this protein are stable in the gas phase. The reactivities of the 9+ and 10+ charge state ions, formed by electrospray ionization of "native" (disulfide-intact) and "denatured" (disulfide-reduced) solutions, are consistent with values calculated for ions in their crystal structure and fully denatured conformations, respectively. Charge states below 8+ of both forms, formed by proton stripping, have similar or indistinguishable reactivities, indicating that the disulfide-reduced ions fold in the gas phase to a more compact conformation.     

Tests for comparing images based on randomization and permutation methods

Tests comparing image sets can play a critical role in PET research, providing a yes-no answer to the question "Are two image sets different?" The statistical goal is to determine how often observed differences would occur by chance alone. We examined randomization methods to provide several omnibus test for PET images and compared these tests with two currently used methods. In the first series of analyses, normally distributed image data were simulated fulfilling the requirements of standard statistical tests. These analyses generated power estimates and compared the various test statistics under optimal conditions. Varying whether the standard deviations were local or pooled estimates provided an assessment of a distinguishing feature between the SPM and Montreal methods. In a second series of analyses, we more closely simulated current PET acquisition and analysis techniques. Finally, PET images from normal subjects were used as an example of randomization. Randomization proved to be a highly flexible and powerful statistical procedure. Furthermore, the randomization test does not require extensive and unrealistic statistical assumptions made by standard procedures currently in use.     

Spinal neurilemmomas and neurofibromas: central dot sign in postgadolinium MRI

The MR studies of three histologically proven spinal neurilemmomas and neurofibromas were reviewed retrospectively. There were two benign neurilemmomas (schwannomas) and one neurofibroma. The common characteristic of these cases was a central low intensity focus ("dot") seen on postcontrast T1-weighted imaging. The low intensity foci corresponded histologically to a congeries of changes including edema, microcysts, foam cells, hyalinization of blood vessels, old hemorrhage, and dystrophic calcification.     

Chlorpropamide-induced hypoglycemia: successful treatment with diazoxide

A healthy adolescent boy was treated on two occasions for an overdose of chlorpropamide (Diabinese). Glucose therapy alone was not sufficient to control the hypoglycemia, but the administration of glucose plus diazoxide raised the blood sugar to supranormal levels. A bolus of intravenous glucagon briefly raised the blood sugar level to within normal limits, increased the blood ketones but also augmented insulin secretion. An overdose of sulfonylurea may cause prolonged and fatal hypoglycemia. Rational therapy, both in diabetic and normal persons, is glucose plus an "insulin antagonist." The administration of diazoxide was effective in our patient, substantially reducing the plasma insulin level; this agent may be the "insulin-antagonist" of choice for use in sulfonylurea-induced hypoglycemia.     

The interaction of dietary fibers and cholesterol upon the plasma lipids and lipoproteins, sterol balance, and bowel function in human subjects

To identify any metabolic effects of dietary fiber upon cholesterol metabolism in man, six adult volunteer subjects were fed eucaloric cholesterol-free formula diets, with and without added dietary fiber for two 4-wk periods. A large quantity of dietary fiber was fed, some 60 g of plant cell wall material (or 16 g of crude fiber) derived from corn, beans, bran, pectin, and purified cellulose. This provided about five times the fiber intake of the typical American diet. The addition of fiber to the cholesterol-free diet did not change either the plasma cholesterol level (171+/-21 mg/dl, SEM, to 167+/-18) or the triglyceride (103+/-39 to 93+/-27 mg/dl). The excretion of both endogenous neutral steroids and bile acids were unchanged with fiber (505+/-41 to 636+/-75 mg/day and 194+/-23 to 266+/-47 mg/day, respectively.) However, total fecal steroid excretion was increased 699+/-29 to 902+/-64 mg/day, P < 0.025). With fiber, intestinal transit time was decreased (59+/-9 to 35+/-8 h, P < 0.005), and both the wet and dry stool weights were greatly increased.A second group of six subjects was fed similar diets containing 1,000 mg cholesterol derived from egg yolk. The addition of fiber to the 1,000-mg cholesterol diet did not alter either plasma cholesterol level (233+/-26 to 223+/-36 mg/dl) or triglyceride (102+/-19 to 83+/-11 mg/dl). The excretion of endogenous neutral steroids (618+/-84 to 571+/-59 mg/day), of bile acids (423+/-122 to 401+/-89 mg/day), and of total fecal steroids (1,041+/-175 to 972+/-111 mg/day) were unchanged by fiber. The absorption of dietary cholesterol was not altered when fiber was added to the 1,000-mg cholesterol diet (44.0+/-3.3 to 42.9+/-2.5%). A two-way analysis of variance utilizing both groups of subjects indicated a significant (P < 0.001) effect of dietary cholesterol upon the plasma cholesterol concentration. We concluded that a large quantity of dietary fiber from diverse sources had little or no effect upon the plasma lipids and sterol balance in man in spite of the fact that intestinal transit time and stool bulk changed greatly.     

Folding pathway of a lattice model for proteins

The folding of a protein-like heteropolymer is studied by using direct simulation of a lattice model that folds rapidly to a well-defined "native" structure. The details of each molecular folding event depend on the random initial conformation as well as the random thermal fluctuations of the polymer. By analyzing the statistical properties of hundreds of folding events, a classical folding "pathway" for such a polymer is found that includes partially folded, on-pathway intermediates that are shown to be metastable equilibrium states of the polymer. These results are discussed in the context of the "classical" and "new" views of folding.     

Kinematic data on primate head and neck posture: implications for the evolution of basicranial flexion and an evaluation of registration planes used in paleoanthropology

Kinematic data on primate head and neck posture were collected by filming 29 primate species during locomotion. These were used to test whether head and neck posture are significant influences on basicranial flexion and whether the Frankfurt plane can legitimately be employed in paleoanthropological studies. Three kinematic measurements were recorded as angles relative to the gravity vector, the inclination of the orbital plane, the inclination of the neck, and the inclination of the Frankfurt plane. A fourth kinematic measurement was calculated as the angle between the neck and the orbital plane (the head-neck angle [HNA]). The functional relationships of basicranial flexion were examined by calculating the correlations and partial correlations between HNA and craniometric measurements representing basicranial flexion, orbital kyphosis, and relative brain size (Ross and Ravosa [1993] Am. J. Phys. Anthropol. 91:305-324). Significant partial correlations were observed between relative brain size and basicranial flexion and between HNA and orbital kyphosis. This indicates that brain size, rather than head and neck posture, is the primary influence on flexion, while the degree of orbital kyphosis may act to reorient the visual field in response to variation in head and neck posture. Regarding registration planes, the Frankfurt plane was found to be horizontal in humans but inclined in all nonhuman primates. In contrast, nearly all primates (including humans) oriented their orbits such that they faced anteriorly and slightly inferiorly. These results suggest that for certain functional craniometric studies, the orbital plane may be a more suitable registration plane than Frankfurt "Horizontal."     

Cultural factors related to the peer review of teaching

Since 1994, the American Association for Higher Education Peer Review of Teaching Project has sought to popularize the notion that teaching is both a scholarly activity and community property to be shared with and critiqued by the larger academic community. In order to accomplish these goals, each of the three academic units at the twelve participating universities developed a pilot project that conformed to its own institutional, academic unit, and disciplinary culture. At a large Midwestern university, the academic units of mathematics, history, and nursing developed different projects. Each of these projects took account of the unit's specific culture, and this fact helps to account, in large part, for each project's success.