Extent and mechanism of sealing in transected giant axons of squid and earthworms

Transected axons are often assumed to seal at their cut ends by the formation of continuous membrane barriers that allow for the restoration of function in the axonal stumps. We have used several electrophysiological measures (membrane potential, input resistance, injury current density) and several morphological measures (phase-contrast, video-enhanced differential interference contrast, light, and electron microscopies) of living and fixed material to assess the extent and mechanism of sealing within hours after transecting giant axons of squid (Loligo pealeiand Sepioteuthis lessoniana) and earthworms (Lumbricus terrestris). Our electrophysiological data suggest that the proximal and distal ends of transected squid giant axons do not completely seal within 2.5 hr in physiological saline. In contrast, the same set of measures suggest that proximal and distal ends of transected earthworm giant axons seal within 1 hr in physiological saline. Our morphological data show that the cut ends of both squid and earthworm axons constrict, but that a 20- 70-am-diameter opening always remains at the cut end that is filled with vesicles. Axonal transection induces the formation of vesicles that are observed in the axoplasm within minutes in standard salines and that rapidly migrate to the cut ends. These injury-induced vesicles are loosely packed near the cut ends of squid giant axons, which do not functionally seal within 2.5 hr of transection. In contrast, vesicles formed a tightly packed plug at the cut ends of earthworm medial giant axons, which do functionally seal within 1 hr of transection in physiological saline. Since we detect no single continuous membrane that spans the cut end, sealing does not appear to occur by the fusion of constricted axolemmal membrane or the formation of a membranous partition at the cut end. Rather, our data are consistent with the hypothesis that a tightly packed vesicular plug is responsible for sealing of earthworm giant axons.This work was supported in part by NIH Grant NS31256 and ONR Grant N00014-90-J-1137 to H.M.F., an NIAAA fellowship to T.L.K., and an ATP grant to G.D.B.Neuroscienc

Can Geometric Test Probe the Cosmic Equation of State ?

Feasibility of the geometric test as a probe of the cosmic equation of state of the dark energy is discussed assuming the future 2dF QSO sample. We examine sensitivity of the QSO two-point correlation functions, which are theoretically computed incorporating the light-cone effect and the redshift distortions, as well as the nonlinear effect, to a bias model whose evolution is phenomenologically parameterized. It is shown that the correlation functions are sensitive on a mean amplitude of the bias and not to the speed of the redshift evolution. We will also demonstrate that an optimistic geometric test could suffer from confusion that a signal from the cosmological model can be confused with that from a stochastic character of the bias.Comment: 11 pages, including 3 figures, accepted for publication in ApJ

p38 MAP kinase mediated proteoglycan synthesis as a target for the prevention of atherosclerosis

The major underlying pathology of most cardiovascular disease is the chronic inflammatory disease of atherosclerosis. Type 2 diabetes, also recognised as an inflammatory condition, accelerates the development of atherosclerosis. Current therapies for atherosclerosis target risk factors such as elevated blood lipids and hypertension and are of strong but limited efficacy. The "response to retention" hypothesis states that atherosclerosis is initiated by the accumulation of lipids through binding to extracellular matrix, and this is specifically the glycosaminoglycan (GAG) chains on proteoglycans. Many vasoactive agonists stimulate changes in the structure of the GAGs which increase lipid binding and the relevant signalling pathways are a potential therapeutic target. It has recently been demonstrated that the actions of transforming growth factor b; on vascular smooth muscle proteoglycan synthesis involves signalling through p38 MAP kinase and inhibition of this pathway reduces binding of lipids. Inhibition of p38 MAP kinase will elicit a wide spread antiinflammatory response which may alleviate some of the deleterious processes in cardiovascular tissues. This article explores the potential for the actions of p38 MAP kinase inhibitors directed at proteoglycan synthesis in vascular smooth muscle to contribute to the beneficial outcomes from targeting p38 MAP kinase for the prevention of cardiovascular disease

Calcific aortic valve disease and hypertension

This review addresses the role of hypertension in precipitating Calcific aortic valve disease (CAVD) and the therapeutic potential of anti-hypertensive interventions to ameliorate CAVD. CAVD was originally considered to be a degenerative disease representing the "wear and tear" of the aortic valves. More recently both conceptually and experimentally, CAVD has come to be considered the result of an active disease process, Whilst, there are some common factors in the pathology and risk factors for atherosclerosis and CAVD there are also some distinct differences. Hypertension is an established risk factor for coronary artery disease and has been recognised as a risk factor for CAVD. Angiotensin converting enzyme inhibitors have been found to have beneficial effects in CAVD and as in atherosclerosis such effects may be due to the blood pressure lowering action but also to direct pleiotropic effects on the biochemical and cellular mechanisms of disease progression in the respective tissues. The very high prevalence of hypertension in the community coupled with an aging population, a risk factor associated with both hypertension and CAVD, infers that hypertension will be one of the predominant factors that increase the impact of CAVD on human health in the coming decades

The Gravitational Lensing in Redshift-space Correlation Functions of Galaxies and Quasars

The gravitational lensing, as well as the velocity field and the cosmological light-cone warp, changes the observed correlation function of high-redshift objects. We present an analytical expression of 3D correlation function, simultaneously including those three effects. When two objects are separated over several hundreds Mpc along a line of sight, the observed correlation function is dominated by the effect of gravitational lensing rather than the intrinsic clustering. For a canonical lambda-CDM model, the lensing signals in the galaxy-galaxy and galaxy-QSO correlations are beyond noise levels in large-scale redshift surveys like the Sloan Digital Sky Survey.Comment: 10 pages, 1 figure, submitted to ApJ

Impact of Universal Social-Emotional and Behavioral Screening Among Middle School Students: A Multistage Approach to Identification

Mental health problems often have an onset during the school age years and significantly impact the development, academic achievement, and future success of children and adolescents (Kessler et al., 2005). Less than half of the 10% to 20% of youth believed to be emotionally and behaviorally at-risk receive the mental health services they need (Bradshaw et al., 2008; Gresham, 2007). As a result, universal screening for mental health risk has been recommended as the best initial step to identifying and intervening with at-risk students. Numerous screeners and methods of implementation exist, but a widely accepted and utilized process has failed to emerge. This study investigated a multistage approach to universal emotional and behavioral screening of adolescents in secondary schools utilizing self-report measures of the Behavioral and Emotional Screening System (BESS) and Behavior Assessment System for Children, Second Edition (BASC-2). Specifically, the relationship between level of risk for emotional and behavioral difficulties and various demographic variables including gender, ethnicity, language status, and special education status were examined. The participants consisted of 358 eighth grade students. Results found approximately 17% of students rated themselves in the at-risk range for emotional and behavioral difficulties on the BESS. Significantly more females rated themselves as at-risk for behavioral and emotional risk. Contrary to expectations, males and females did not rate themselves significantly different in the types of behavioral problems they were experiencing. Severity ratings of risk on the BESS administered at Stage 1 were consistent with the results of the BASC-2, the comprehensive behavioral assessment administered at Stage 2. Students identified with the most risk on the BESS endorsed more clinically significant maladaptive behaviors and less adjustment or functional skills on the BASC-2 than students with less measured risk. Overall, at-risk students reported negative feelings about school and themselves, difficulty with attention and focus, difficulties with parents, inability to solve problems, and feelings of sadness, which were most likely significantly impacting their ability to be successful at school. The present study uncovered a large number of students who appeared to be in imminent need of mental health services, but were not receiving any formal intervention in or out of school. Without implementation of a mental health screening program such as this, students may not be appropriately identified as at-risk for emotional and behavioral problems and therefore, continue to struggle academically, socially, and behaviorally. The comprehensive data collected on at-risk students may ultimately be used to guide and direct future interventions based on a student’s descriptive profile

Comparison of 99mTc-sestamibi and doxorubicin to monitor inhibition of P-glycoprotein function

P-glycoprotein (Pgp) overexpression is a well-recognized factor in resistance to chemotherapy. Doxorubicin flow cytometry is used to monitor Pgp function in haematological specimens and biopsies from other cancers, and radionuclide imaging with sestamibi has recently shown promise for non-invasive monitoring. In the present study the two methods were directly compared in single-cell suspensions of three variants of the human breast carcinoma cell line MCF7: sensitive MCF7/WT, doxorubicin-selected MCF7/AdrR, and MDR1 -gene-transfected MCF7/BC19 cells with doxorubicin resistance factors of 1, 192, and 14, respectively. Accumulation of sestamibi and mean fluorescence of doxorubicin (5.5 μM) were assessed over 60 min in the presence and absence of Pgp modulators GG918 (0.01 to 0.2 μM) and PSC833 (0.05 to 2.0 μM). Accumulation curves for sestamibi and doxorubicin differed among the cell variants under control conditions, with sestamibi showing a significantly greater difference between WT and resistant cells than doxorubicin. Both GG918 and PSC833 reversed uptake deficits to WT levels for sestamibi in MCF7/BC19 cells and doxorubicin in MCF7/BC19 and MCF7/AdrR cells, but failed to show the same effect for sestamibi in MCF7/AdrR cells (∼30% of MCF7/WT level). Thus, both methods clearly distinguished sensitive from resistant MCF7 variants, with the radionuclide method showing greater sensitivity. © 2001 Cancer Research Campaign http://www.bjcancer.co