COMPARISON OF DNA RENEWAL IN GERM-FREE AND CONVENTIONAL MICE USING [125I]IODODEOXYURIDINE AND [3H]THYMIDINE

Germ-free (GF) and conventional (CV) C3H mice received a single injection of 1 μCi [³H]thymidine and 3 μCi [¹²⁵I]iododeoxyuridine to provide simultaneous labeling of DNA with the two precursors. Thymus, spleen, mesenteric lymph nodes, bone marrow (femora), small intestine, colon and skin were examined for total organ activity and rate of DNA renewal 1–8 days after injection. Precursor incorporation, assayed on day 1, was lower in the thymus, mesenteric lymph nodes and femora (and, to a lesser extent, in the spleen and colon) of GF mice as compared to CV animals. The opposite was observed in the small intestine and skin, i.e. total organ activity was higher in GF animals. Differences in precursor incorporation were partly due to differences in organ weights between the two groups of mice. In comparison to CV animals, DNA renewal rates were diminished in the mesenteric lymph nodes, bone marrow, colon (following a 3-day plateau) and spleen of GF mice. Little, if any, difference was observed between the two groups with respect to the rate of DNA turnover in the thymus and skin. Radioactivity of the small intestine remained constant for 2 days. Thereafter intestinal activity in GF mice declined at an initial slow rate between days 2 and 5 followed by a rapid decrease between days 5 and 8. In CV mice the first phase of activity loss was short with the rapid decline in intestinal activity beginning on day 3. From the slopes of the regression lines, the percentage thymidine reutilization was estimated. Reutilization varied from 0 to 63% in the various organs examined, with the greatest difference between GF and CV mice occurring in the mesenteric lymph nodes.     

Associations between White Matter Hyperintensities and β Amyloid on Integrity of Projection,Association, and Limbic Fiber Tracts Measured with Diffusion Tensor MRI

The goal of this study was to assess the relationship between Aβ deposition and white matter pathology (i.e., white matter hyperintensities, WMH) on microstructural integrity of the white matter. Fifty-seven participants (mean age: 78±7 years) from an ongoing multi-site research program who spanned the spectrum of normal to mild cognitive impairment (Clinical dementia rating 0–0.5) and low to high risk factors for arteriosclerosis and WMH pathology (defined as WMH volume >0.5% total intracranial volume) were assessed with positron emission tomography (PET) with Pittsburg compound B (PiB) and magnetic resonance and diffusion tensor imaging (DTI). Multivariate analysis of covariance were used to investigate the relationship between Aβ deposition and WMH pathology on fractional anisotropy (FA) from 9 tracts of interest (i.e., corona radiata, internal capsule, cingulum, parahippocampal white matter, corpus callosum, superior longitudinal, superior and inferior front-occipital fasciculi, and fornix). WMH pathology was associated with reduced FA in projection (i.e., internal capsule and corona radiate) and association (i.e., superior longitudinal, superior and inferior fronto-occipital fasciculi) fiber tracts. Aβ deposition (i.e., PiB positivity) was associated with reduced FA in the fornix and splenium of the corpus callosum. There were interactions between PiB and WMH pathology in the internal capsule and parahippocampal white matter, where Aβ deposition reduced FA more among subjects with WMH pathology than those without. However, accounting for apoE ε4 genotype rendered these interactions insignificant. Although this finding suggests that apoE4 may increase amyloid deposition, both in the parenchyma (resulting in PiB positivity) and in blood vessels (resulting in amyloid angiopathy and WMH pathology), and that these two factors together may be associated with compromised white matter microstructural integrity in multiple brain regions, additional studies with a longitudinal design will be necessary to resolve this issue.     

How can the functional reponse best be determined?

Summary We evaluated three methods for the analysis of functional response data by asking whether a given method could discriminate among functional responses and whether it could accurately identify regions of positive density-dependent predation. We evaluated comparative curve fitting with foraging models, linear least-squares analysis using the angular transformation, and logit analysis. Using data from nature and simulations, we found that the analyses of predation rates with the angular transformation and logit analysis were best at consistently determining the true functional response, i.e. the model used to generate simulated data. These methods also produced the most accurate estimates of the true regions of density dependence. Of these two methods, functional response data best fulfill the assumptions of logit analysis. Angularly transformed predation rates only approximate the assumptions of linear leastsquares analysis for predation rates between 0.1 and 0.9. Lack-of-fit statistics can reveal inadequate fit of a model to a data set where simple regression statistics might erroneously suggest a good match.     

A semiempirical study of the prototropic tautomerism of hypoxanthine

The total and relative energies, bond order matrices and localized MOs for the eight possible tautomers of hypoxanthine (HYP) have been calculated, with full geometry optimization, using both AM1 and MNDO methods. The AM1 relative energies show that HYP(9,1), HYP(7,1) and HYP (9,10) are the predominant species at room temperature, the two former being in larger concentration that the latter. The calculated IR spectra for these species agree well with the reported spectrum in an isolated matrix, which has been interpreted in terms of the presence of these three tautomeric forms. The MNDO method does not predict the right order, and the more stable tautomer would be HYP(9,10). The calculated structure for the HYP(9,1) species shows that the molecule is essentially planar. The bond distances compare well with those of hypoxanthine hydrochloride and guanine and also correlate well with the calculated bond orders. The proton affinities for the three more stable tautomers have also been calculated. For HYP(9,1) the prefered site of protonation is N7, whereas for HYP(7,1) the protonation occurs rather at N9. These results agree well with¹⁵N and¹³C NMR studies in DMSO.     

Hunter syndrome in Jews in Israel: further evidence for prenatal selection favoring the Hunter allele

Summary Among all the Jewish families with Hunter patients in Israel, 10 were Ashkenazi or Moroccan in origin. In those families, there was a paucity of new mutations. In addition, a significant deviation of the segregation ratio between the Hunter gene and the normal allele was demonstrated among the offspring of heterozygous mothers or siblings of affected children in these families. These results confirm and extend our previous observations suggesting selection in favor of the X chromosome carrying the Hunter allele among Ashkenazi and Moroccan Jews.     

Thermal ecology of Pieris butterflies (Lepidoptera: Pieridae): a new mechanism of behavioral thermoregulation

Summary I document a new mechanism for behavioral thermoregulation, not previously described in animals, called reflectance basking. This behavior, described here for Pieris butterflies, involves the use of the wings as solar reflectors that reflect solar radiation onto the body to increase body temperature. Results show that Pieris require thoracic (body) temperature. between 29° and 40° C in order to take off and fly, and achieve these elevated temperatures by basking. Diurnal patterns of population flight activity are closely correlated with patterns of body temperature during basking. Behavioral studies indicate that 1) Pieris orient to solar radiation, 2) they use thermoregulatory postures consistent with reflectance basking, and 3) they do not use the basking postures found in other Pierid butterflies (i.e., the Coliadinae). There are consistent differences in wing angles used in reflectance basking between Pieris in different subgenera. Results are discussed with respect to thermoregulation and wing color in other Pierid butterflies, and suggest that a re-evaluation of the functional significance of melanization in Pieris is needed.     

Retention of ingested latex particles in Peyer's patches of germfree and conventional mice

Conventional and germfree mice ingested a suspension of 2-micron latex particles in drinking water for a 15-day period. Number and distribution of intestinal Peyer's patches did not differ significantly in the two types of mice. Cleared Peyer's patches were compared with regard to size and particle content. The location of particles within Peyer's patch follicles of germfree mice was similar to that of conventional mice, but the latter had significantly larger follicles and greater accumulations of latex particles. Latex concentration varied with patch location. Proximal patches contained the majority of particles in germfree mice, whereas particles were most abundant in distal patches of conventional mice. The results show that particle uptake into Peyer's patches takes place even in the complete absence of bacteria in the gut.     

Exogenous gangliosides enhance the interaction of fibronectin with ganglioside-deficient cells

The major cell-surface glycoprotein fibronectin mediates a variety of cellular adhesive interactions that have been reported to be competitively inhibited by gangliosides. These effects suggest a possible function of gangliosides as receptors for fibronectin. To test this hypothesis more directly, we examined the interaction of endogenous fibronectin with a ganglioside-deficient cell line, NCTC 2071. These cells, which grow in serum-free medium, synthesized fibronectin. The fibronectin did not bind to these cells, but instead bound diffusely to the culture substratum. When the cells were cultured in medium containing ganglioside, the fibronectin became bound to the cell surface in fibrillar strands. The order of effectiveness of purified gangliosides was GT1b greater than GD1a greater than GM1 greater than GM2 greater than GM3. The effect with mixed gangliosides was accompanied by a restoration of cellular capacity to bind and to respond to cholera toxin. Treatment of the cells with several phospholipids did not alter fibronectin binding. Our results support the hypothesis that gangliosides can help mediate the binding of fibronectin to fibroblasts.