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.     

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.     

Inhibition of cytochrome P-450 3A (CYP3A) in human intestinal and liver microsomes: comparison of Ki values and impact of CYP3A5 expression

Seckel syndrome has been described as the prototype of the primordial bird-headed type of dwarfism. Since Seckel originally defined the disorder, less than 60 cases have been reported. In addition to the characteristic craniofacial dysmorphism and skeletal defects, abnormalities have been described in the cardiovascular, hematopoietic, endocrine, and central nervous systems. This pleiotropy has implied genetic heterogeneity and prompted reviews of previously reported cases of Seckel syndrome. As a result, the characteristic diagnostic features of Seckel syndrome have been highly debated. Although deletions in chromosome 2q have been described, to date, no genetic defect has been defined. We report three cases of Seckel-like syndrome in siblings from nonconsanguinous Caucasian parents. In addition to the typical Seckel phenotypic features, all three cases were characterized by severe hydrocephalus. We review the literature and propose that there is a spectrum of Seckel conditions that share some common key features, but also demonstrate a wide range of phenotypic features.     

Mechanical transport of rotavirus by the legs and wings of Musca domestica (Diptera: Muscidae)

BACKGROUND: Whether or not tumor response to chemotherapy-sensitized radiation therapy (CTRT) for head and neck cancer leads to an improved outcome is unknown. METHODS: Forty patients who received preoperative cisplatin plus simultaneous radiotherapy for operable stage III and IV head and neck cancer were reviewed retrospectively regarding clinical demographics, staging, and survival status. RESULTS: Twenty-one (57%) patients had a histologic complete response (HCR) and 16 (43%) had a partial (PR) (9) or clinical complete (7) response (CCR). Tumor response of N1 versus N2-3 nodal disease showed 6 (75%) HCR and 4 (25%). Five-year disease-free survival overall was 82% for HCR versus 38% for PR/CCR (P <0.05). Disease-specific 5-year survival was 100% for HCR versus 27% for PR/CCR (P <0.002). CONCLUSIONS: Histologic complete response to CTRT for head and neck cancer is associated with increased survival and encouraging disease-free status. Response to CTRT is inversely proportional to lymphatic tumor load.     

The nitric oxide synthase inhibitor L-NAME (N omega-nitro-L-arginine methyl ester) does not produce discriminative stimulus effects similar to ethanol

Three key aspects of Florence Nightingale remarkable life are examine. First, the influence during her formative years: the education and guidance provided by her father, the resistance by her family when she decided to become a nurse; and the rejection by Nightingale of the societal expectations of a woman in the Victorian era. Secondly, her professional life is examined, in particular how she appears to have been viewed by certain members of society, and how it turn she viewed them. It is anticipated that her position as an early feminist will be postulated and illuminated. Thirdly, an analysis of her personal and professional life indicates a way forward for the nursing profession.     

Binding kinetics of monoclonal antibody using antigen-beta-galactosidase hybrid protein: application to measurement of peptide antigenicity

A simple method for determination of binding kinetics of a solid-phase antibody using antigen-beta-galactosidase hybrid protein was evaluated. To minimize conformational change of the antigen binding site of the antibody when directly binding to a microtiter plate, the microtiter plate was precoated with protein A. The binding and free antigen concentrations were directly obtained from the beta-galactosidase activity. This method can be used for analyses of the equilibrium dissociation constant (KD), and the association (Kass) and dissociation (Kdiss) rate constants. Peptide antigenicity was also analyzed by competitive ELISA using this method. Since both antigen-beta-galactosidase and the peptide used are localized in the fluid-phase, the proper affinity constant (KA) of the peptide can be estimated from the KD value of the antigen-beta-galactosidase-antibody interaction, and from the IC50 value of the peptide.     

Collision-induced signal enhancement: a method to increase product ion intensities in MS/MS and MSn experiments

Collision-induced signal enhancement (CISE), a new technique to enhance the MSn capabilities of the quadrupole ion trap, is demonstrated. CISE is based on the chemistry, i.e., the dissociation pathways, of the analyte examined. Polysaccharides up to hexamers are used to demonstrate the capabilities of CISE to enhance signal in two distinct functional modes. Mode 1 CISE is designed to enhance the signal of an ion desired for MSn analysis. Mode 2 CISE is designed to enhance structurally significant product ions in an MS/MS spectrum. Two different approaches can be utilized to effect the two functional modes of CISE. Both approaches use conventional resonant excitation techniques to effect dissociation, which is performed nonanalytically, i.e., without isolation of the ions to be dissociated. The two approaches are (1) single-frequency resonance excitation, and (2) broad-band wave form resonant excitation. Experimental results for Mode 1 CISE analysis demonstrate up to a 17.3-fold signal increase for the single-frequency approach and 5.3-fold using broad-band excitation. Mode 2 CISE analysis shows up to a 16.3-fold increase in signal strength with single-frequency excitation and 3.3-fold using broad-band excitation.     

Three-dimensional ultrastructural analysis of the Saccharomyces cerevisiae mitotic spindle

The three dimensional organization of microtubules in mitotic spindles of the yeast Saccharomyces cerevisiae has been determined by computer-aided reconstruction from electron micrographs of serially cross-sectioned spindles. Fifteen spindles ranging in length from 0.6-9.4 microns have been analyzed. Ordered microtubule packing is absent in spindles up to 0.8 micron, but the total number of microtubules is sufficient to allow one microtubule per kinetochore with a few additional microtubules that may form an interpolar spindle. An obvious bundle of about eight interpolar microtubules was found in spindles 1.3-1.6 microns long, and we suggest that the approximately 32 remaining microtubules act as kinetochore fibers. The relative lengths of the microtubules in these spindles suggest that they may be in an early stage of anaphase, even though these spindles are all situated in the mother cell, not in the isthmus between mother and bud. None of the reconstructed spindles exhibited the uniform populations of kinetochore microtubules characteristic of metaphase. Long spindles (2.7-9.4 microns), presumably in anaphase B, contained short remnants of a few presumed kinetochore microtubules clustered near the poles and a few long microtubules extending from each pole toward the spindle midplane, where they interdigitated with their counterparts from the other pole. Interpretation of these reconstructed spindles offers some insights into the mechanisms of mitosis in this yeast.     

Aggregation and motor neuron toxicity of an ALS-linked SOD1 mutant independent from wild-type SOD1

Analysis of transgenic mice expressing familial amyotrophic lateral sclerosis (ALS)-linked mutations in the enzyme superoxide dismutase (SOD1) have shown that motor neuron death arises from a mutant-mediated toxic property or properties. In testing the disease mechanism, both elimination and elevation of wild-type SOD1 were found to have no effect on mutant-mediated disease, which demonstrates that the use of SOD mimetics is unlikely to be an effective therapy and raises the question of whether toxicity arises from superoxide-mediated oxidative stress. Aggregates containing SOD1 were common to disease caused by different mutants, implying that coaggregation of an unidentified essential component or components or aberrant catalysis by misfolded mutants underlies a portion of mutant-mediated toxicity.     

Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat

Conjugated linoleic acid (CLA) is a naturally occurring fatty acid which has anti-carcinogenic and anti-atherogenic properties. CLA activates PPAR alpha in liver, and shares functional similarities to ligands of PPAR gamma, the thiazolidinediones, which are potent insulin sensitizers. We provide the first evidence that CLA is able to normalize impaired glucose tolerance and improve hyperinsulinemia in the pre-diabetic ZDF rat. Additionally, dietary CLA increased steady state levels of aP2 mRNA in adipose tissue of fatty ZDF rats compared to controls, consistent with activation of PPAR gamma. The insulin sensitizing effects of CLA are due, at least in part, to activation of PPAR gamma since increasing levels of CLA induced a dose-dependent transactivation of PPAR gamma in CV-1 cells cotransfected with PPAR gamma and PPRE X 3-luciferase reporter construct. CLA effects on glucose tolerance and glucose homeostasis indicate that dietary CLA may prove to be an important therapy for the prevention and treatment of NIDDM.