Cleavage experiments with deoxythymidine 3'',5''-bis-(p-nitrophenyl phosphate) suggest that the homing endonuclease I-PpoI follows the same mechanism of phosphodiester bond hydrolysis as the non-specific Serratia nuclease

The present study examined the effects of morphine in pigeons responding under a progressive-ratio 25 schedule of food delivery. Morphine initially reduced response rates and breaking points. With chronic exposure, tolerance developed to these effects. The magnitude of the observed tolerance was not obviously different from that previously reported under a PR 5 schedule of food delivery. In addition, when drug effects were compared under the fixed-ratio 25 and fixed-ratio 100 components comprised by the progressive-ratio schedule, comparable tolerance was observed. Although prior studies using other procedures have shown that ratio size modulates the development of tolerance to morphine and other drugs, the present data suggest that this relation is constrained, and is not easily observed under progressive-ratio schedules.     

Geographic variation in the calls of wild chimpanzees: a reassessment

Male chimpanzees produce a species-typical call, the pant hoot, to communicate to conspecifics over long-distances. Calls given by males from the well-known Gombe and Mahale populations typically consist of four different phases: an introduction, build-up, climax, and let-down. Recent observations suggest that chimpanzees living in the Kibale National Park, Uganda, consistently give calls that lack a build-up and are thus qualitatively distinguishable acoustically from those made by other East African conspecifics. We analyzed additional recordings from Mahale and Kibale to re-examine geographic variation in chimpanzee calls. Results indicate that males from both sites produce pant hoots containing all four parts of the call. Calls made by chimpanzees from the two populations, however, differ in quantitative acoustic measures. Specifically, males at Kibale initiate their calls with significantly longer elements and build-up over briefer periods at slower rates than individuals from Mahale. Kibale males also deliver acoustically less variable calls than chimpanzees at Mahale. Although climax elements do not differ between populations in any single acoustic feature, discriminant function analysis reveals that acoustic variables can be used in combination to assign calls to the correct population at rates higher than that expected by chance. Ecological factors related to differences in habitat acoustics, the sound environment of the local biota, and body size are likely to account for these observed macrogeographic variations in chimpanzee calls.     

Imaging of the pediatric orbit and visual pathways: computed tomography and magnetic resonance imaging

Tumors of the small bowel are uncommon and seldom suspected on a clinical basis. Together with the relative inaccessibility of the small bowel to endoscopic investigation, the rarity of these tumors undoubtedly delays the diagnosis. Small bowel tumors may be an interesting field of application for enteroscopy, which now can be readily performed with dedicated enteroscopic evaluation in patients with suspected small bowel neoplasia could improve prognosis and treatment. Enteroscopy may also play an important role in the surveillance of inherited polyposis syndromes, as in other precancerous condition of the small bowel. In Peutz-Jeghers syndrome it may reduce polyp-induced complications and improve planning for surgery; in familial adenomatous polyposis it may contribute to preventing upper gastrointestinal tract cancer.     

The trithorax group gene moira encodes a brahma-associated putative chromatin-remodeling factor in Drosophila melanogaster

The genes of the trithorax group (trxG) in Drosophila melanogaster are required to maintain the pattern of homeotic gene expression that is established early in embryogenesis by the transient expression of the segmentation genes. The precise role of each of the diverse trxG members and the functional relationships among them are not well understood. Here, we report on the isolation of the trxG gene moira (mor) and its molecular characterization. mor encodes a fruit fly homolog of the human and yeast chromatin-remodeling factors BAF170, BAF155, and SWI3. mor is widely expressed throughout development, and its 170-kDa protein product is present in many embryonic tissues. In vitro, MOR can bind to itself and it interacts with Brahma (BRM), an SWI2-SNF2 homolog, with which it is associated in embryonic nuclear extracts. The leucine zipper motif of MOR is likely to participate in self-oligomerization; the equally conserved SANT domain, for which no function is known, may be required for optimal binding to BRM. MOR thus joins BRM and Snf5-related 1 (SNR1), two known Drosophila SWI-SNF subunits that act as positive regulators of the homeotic genes. These observations provide a molecular explanation for the phenotypic and genetic relationships among several of the trxG genes by suggesting that they encode evolutionarily conserved components of a chromatin-remodeling complex.     

Validation of highly polymorphic fluorescent multiplex short tandem repeat systems using two generations of DNA sequencers

Validation studies are a crucial requirement before implementation of new genetic typing systems for clinical diagnostics or forensic identity. Two different fluorescence-based multiplex DNA profiling systems composed of amelogenin, HumD21S11 and HumFGA (referred to as multiplex 1A), and HumD3S1358, HumD21S11 and HumFGA (multiplex 1B) have been evaluated for use in forensic identification using the Applied Biosystems Model 373A and Prism 377 DNA Sequencers, respectively. Experiments were aimed at defining the limit of target DNA required for reliable profiling, the level of degradation that would still permit amplification of the short tandem repeat (STR) loci examined, and the robustness of each locus in the multiplexes after samples were exposed to environmental insults. In addition, the specificity of the multiplexes was demonstrated using nonhuman DNAs. Forensically relevant samples such as cigarette butts, chewing gum, fingernails and envelope flaps were processed using both an organic extraction procedure and a QIAamp protocol. DNAs and resultant multiplex STR profiles were compared. The validation of the triplex STR systems was extended to include over 140 nonprobative casework specimens and was followed with a close monitoring of initial casework (over 300 exhibits). Our results document the robustness of these multiplex STR profiling systems which, when combined with other multiplex systems, could provide a power of discrimination of approximately 0.9999.     

Heritability of anxiety sensitivity: a twin study

OBJECTIVE: In attempting to explain the familial predisposition to panic disorder, most studies have focused on the heritability of physiologic characteristics (e.g., CO2 sensitivity). A heretofore unexplored possibility is that a psychological characteristic that predisposes to panic-anxiety sensitivity-might be inherited. In this study, the authors examined the heritability of anxiety sensitivity through use of a twin group. METHOD: Scores on the Anxiety Sensitivity Index were examined in a group of 179 monozygotic and 158 dizygotic twin pairs. Biometrical model fitting was conducted through use of standard statistical methods. RESULTS: Broad heritability estimate of the Anxiety Sensitivity Index as a unifactorial construct was 45%. Additive genetic effects and unique environmental effects emerged as the primary influences on anxiety sensitivity. There was no evidence of genetic discontinuity between normal and extreme scores on the Anxiety Sensitivity Index. CONCLUSIONS: This study suggests that one psychological risk factor for the development of panic disorder-anxiety sensitivity-may have a heritable component. As such, anxiety sensitivity should be considered in future research on the heritability of panic disorder.     

Use of a gonadotropin-releasing hormone agonist in the evaluation of postmenopausal virilization due to ovarian hyperthecosis. A case report

BACKGROUND: Hyperthecosis in a postmenopausal woman is a very rare cause of virilization, and only five cases have been reported previously. CASE: A woman presented with a nine-year history of increasing hirsutism and a mild virilization beginning in the perimenopausal period. Initial androgen metabolite concentrations suggested attenuated late-onset adrenal hyperplasia, but a trial of dexamethasone treatment was ineffective. Subsequent use of leuprolide acetate resulted in a biochemical and clinical improvement in the signs and symptoms. CONCLUSION: This case is unique because gonadotropin-releasing hormone agonist administration was utilized as both a diagnostic and therapeutic modality.     

Characterization of the specificities of human blood group H gene-specified alpha 1,2-L-fucosyltransferase toward sulfated/sialylated/fucosylated acceptors: evidence for an inverse relationship between alpha 1,2-L-fucosylation of Gal and alpha 1,6-L-fucosylation of asparagine-linked GlcNAc

The assembly of complex structures bearing the H determinant was examined by characterizing the specificities of a cloned blood group H gene-specified alpha 1,2-L-fucosyltransferase (FT) toward a variety of sulfated, sialylated, or fucosylated Gal beta 1,3/4GlcNAc beta- or Gal beta 1,3GalNAc alpha-based acceptor structures. (a) As compared to the basic type 2, Gal beta 1,4GlcNAc beta-(K(m) = 1.67 mM), the basic type 1 was 137% active (K(m) = 0.83 mM). (b) On C-6 sulfation of Gal, type 1 became 142.1% active and type 2 became 223.0% active (K(m) = 0.45 mM). (c) On C-6 sulfation of GlcNAc, type 2 showed 33.7% activity. (d) On C-3 or C-4 fucosylation of GlcNAc, both types 1 and 2 lost activity. (e) Type 1 showed 70.8% and 5.8% activity, respectively, on C-6 and C-4 O-methylation of GlcNAc. (f) Type 1 retained 18.8% activity on alpha 2,6-sialylation of GlcNAc. (g) Terminal type 1 or 2 of extended chain had lower activity. (h) With Gal in place of GlcNAc in type 1, the activity became 43.2%. (i) Compounds with terminal alpha 1,3-linked Gal were inactive. (j) Gal beta 1,3GalNAc alpha- (the T-hapten) was approximately 0.4-fold as active as Gal beta 1,4GlcNAc beta-. (k) C-6 sulfation of Gal on the T-hapten did not affect the acceptor activity. (l) C-6 sulfation of GalNAc decreased the activity to 70%, whereas on C-6 sulfation of both Gal and GalNAc the T-hapten lost the acceptor ability. (m) C-6 sialylation of GalNAc also led to inactivity. (n) beta 1,6 branching from GalNAc of the T-hapten by a GlcNAc residue or by units such as Gal beta 1, 4GlcNAc-, Gal beta 1,4(Fuc alpha 1,3)GlcNAc-, or 3-sulfoGal beta 1,4GlcNAc- resulted in 111.9%, 282.8%, 48.3%, and 75.3% activities, respectively. (o) The enhancement of enzyme affinity by a sulfo group on C-6 of Gal was demonstrated by an increase (approximately 5-fold) in the K(m) for Gal beta 1,4GlcNAc beta 1,6(Gal beta 1,3)GalNAc alpha-O-Bn in presence of 6-sulfoGal beta 1,- 4GlcNAc beta-O-Me (3.0 mM). (p) Among the two sites in Gal beta 1, 4GlcNAc beta 1,6(Gal beta 1,3) GalNAc alpha-O-Bn, the enzyme had a higher affinity ( > 3-fold) for the Gal linked to GlcNAc. (q) With respect to Gal beta 1,- 3GlcNAc beta-O-Bn (3.0 mM), fetuin triantennary asialo glycopeptide (2.4 mM), bovine IgG diantennary glycopeptide (2.8 mM), asialo Cowper's gland mucin (0.06 mM), and the acrylamide copolymers (0.125 mM each) containing Gal beta 1,3GlcNAc beta-, Gal beta 1,3(6-sulfo)GlcNAc beta-, Gal beta 1,3GalNAc alpha-, Gal beta 1,3Gal beta-, or Gal alpha 1,3Gal beta- units were 153.6%, 43.0%, 6.2%, 52.5%, 94.9%, 14.7%, 23.6%, and 15.6% active, respectively. (r) Fucosylation by alpha 1,2-L-FT of the galactosyl residue which occurs on the antennary structure of the bovine IgG glycopeptide was adversely affected by the presence of an alpha 1,6-L-fucosyl residue located on the distant glucosaminyl residue that is directly attached to the asparagine of the protein backbone. This became evident from the 4-fold activity of alpha 1,2-L-FT toward bovine IgG glycopeptide after approximately 5% removal of alpha 1,6-linked Fuo.