NEW MURID RODENTS FROM THE LATE CENOZOIC OF YUSHE BASIN, SHANXI

<正> As scientific collaborators of the Chinese-American joint project "Neogene Rocks and Faunas, Yushe Basin, Shanxi, PRC", the present authors, with William R. Downs, Northern Arizona University, sampled the Yushe microfauna in the fall of 1987 and 1988. The fossil temains were retrieved by surface collection and by wet-sieving bulk quantities of sediment.     

Clozapine-Induced Mitochondria Alterations and Inflammation in Brain and Insulin-Responsive Cells

Background

Metabolic syndrome (MetS) is a constellation of factors including abdominal obesity, hyperglycemia, dyslipidemias, and hypertension that increase morbidity and mortality from diabetes and cardiovascular diseases and affects more than a third of the population in the US. Clozapine, an atypical antipsychotic used for the treatment of schizophrenia, has been found to cause drug-induced metabolic syndrome (DIMS) and may be a useful tool for studying cellular and molecular changes associated with MetS and DIMS. Mitochondria dysfunction, oxidative stress and inflammation are mechanisms proposed for the development of clozapine-related DIMS. In this study, the effects of clozapine on mitochondrial function and inflammation in insulin responsive and obesity-associated cultured cell lines were examined.

Methodology/Principal Findings

Cultured mouse myoblasts (C2C12), adipocytes (3T3-L1), hepatocytes (FL-83B), and monocytes (RAW 264.7) were treated with 0, 25, 50 and 75 µM clozapine for 24 hours. The mitochondrial selective probe TMRM was used to assess membrane potential and morphology. ATP levels from cell lysates were determined by bioluminescence assay. Cytokine levels in cell supernatants were assessed using a multiplex array. Clozapine was found to alter mitochondria morphology, membrane potential, and volume, and reduce ATP levels in all cell lines. Clozapine also significantly induced the production of proinflammatory cytokines IL-6, GM-CSF and IL12-p70, and this response was particularly robust in the monocyte cell line.

Conclusions/Significance

Clozapine damages mitochondria and promotes inflammation in insulin responsive cells and obesity-associated cell types. These phenomena are closely associated with changes observed in human and animal studies of MetS, obesity, insulin resistance, and diabetes. Therefore, the use of clozapine in DIMS may be an important and relevant tool for investigating cellular and molecular changes associated with the development of these diseases in the general population.     

Practice advisory on liposuction

COMMITTEE STATEMENT: At the 69th annual meeting of the American Society of Plastic Surgeons (ASPS) in October of 2000, the ASPS Board of Directors convened the Task Force on Patient Safety in Office-Based Surgery Facilities. The task force was assembled in the wake of several highly publicized patient deaths involving plastic surgery and increasing state legislative and regulatory activity of office-based surgery facilities. In response to the increased scrutiny of the office-based surgery setting, the task force produced two practice advisories: "Procedures in the Office-Based Surgery Setting" and "Patient Selection in the Office-Based Surgery Setting." Since the task force's inception, professional and public awareness of patient safety issues has continued to grow. This heightened interest resulted in an increased need for plastic surgeons to communicate their views on the topic. To meet this challenge, the task force evolved into the Committee on Patient Safety, allowing the committee to address topics affecting the safety and welfare of plastic surgery patients, regardless of the facility setting. The "Practice Advisory on Liposuction" is the first advisory developed since the committee was formed. It was a lengthy and painstaking process for the committee, which included representatives from related plastic surgery organizations as well as the American Society of Anesthesiologists (ASA). Committee members included Ronald E. Iverson, M.D., chair; Jeffery L. Apfelbaum, M.D., ASA representative; Bruce L. Cunningham, M.D., ASPS/Plastic Surgery Educational Foundation (PSEF) Joint Outcomes Task Force representative; Richard A. D'Amico, M.D., ASPS representative; Victor L. Lewis, Jr., M.D., ASPS Health Policy Analysis Committee representative; Dennis J. Lynch, M.D., ASPS representative; Noel B. McDevitt, M.D., ASPS Deep Vein Thrombosis Task Force representative; Michael F. McGuire, M.D., The American Society for Aesthetic Plastic Surgery (ASAPS) representative; Louis Morales, Jr., M.D., American Society of Maxillofacial Surgeons representative; Calvin R. Peters, M.D., Florida Ad Hoc Commission on Patient Safety representative; Robert Singer, M.D., American Association for Accreditation of Ambulatory Surgery Facilities representative; Thomas Ray Stevenson, M.D., American College of Surgeons representative; Rebecca S. Twersky, M.D., ASA representative; Ronald H. Wender, M.D., ASA representative; and James A. Yates, ASAPS representative. The authors thank members of the committee for the insights they brought to this process. The final document represents their significant contributions to these efforts. They would also like to recognize DeLaine Schmitz and Pat Farrell of the ASPS staff for their work on and support of this project.     

Advanced high school biology in an era of rapid change: a summary of the biology panel report from the NRC Committee on Programs for Advanced Study of Mathematics and Science in American High Schools

A recently released National Research Council (NRC) report, Learning and Understanding: Improving Advanced Study of Mathematics and Science in U.S. High Schools, evaluated and recommended changes in the Advanced Placement (AP), International Baccalaureate (IB), and other advanced secondary school science programs. As part of this study, discipline-specific panels were formed to evaluate advanced programs in biology, chemistry, physics, and mathematics. Among the conclusions of the Content Panel for Biology were that AP courses in particular suffer from inadequate quality control as well as excessive pressure to fulfill their advanced placement function, which encourages teachers to attempt coverage of all areas of biology and emphasize memorization of facts rather than in-depth understanding. In this essay, the Panel's principal findings are discussed, with an emphasis on its recommendation that colleges and universities should be strongly discouraged from using performance on either the AP examination or the IB examination as the sole basis for automatic placement out of required introductory courses for biology majors and distribution requirements for nonmajors.     

Insulin-like and non-insulin-like selenium actions in 3T3-L1 adipocytes

In insulin-sensitive 3T3-L1 adipocytes, selenium stimulates glucose transport and antilipolysis and these actions of selenium, like insulin actions, are sensitive to wortmanin, an inhibitor of phosphatidylinositol-3-kinase (PI3K). Selenium stimulates PI3K activity that is sustained up to 24 h. Selenium after 5-10 min increases tyrosine phosphorylation of selective cellular proteins, but after 24 h overall tyrosine phosphorylation is increased. Tyrosine phosphorylation of insulin receptor substrate 1 is detected when enriched by immunoprecipitation with anti-PI3K antibody. Selenium, however, does not stimulate insulin receptor tyrosine kinase activity. Selenium also increases phosphorylation of other insulin signaling proteins, including Akt and extracellular signal regulated kinases. Selenium-stimulated glucose transport is accompanied by increases in glucose transporter-1 content in the plasma membrane. These data are consistent with similar selenium action in glucose transport in 3T3-L1 fibroblasts expressing mainly GLUT1. In chronic insulin-induced insulin resistant cells, selenium unlike insulin fully stimulates glucose transport. In summary, selenium stimulates glucose transport and antilipolysis in a PI3K-dependent manner, but independent of insulin receptor activation. Selenium exerts both insulin-like and non-insulin-like actions in cells.     

CNTNAP2 is disrupted in a family with Gilles de la Tourette syndrome and obsessive compulsive disorder

Gilles de la Tourette syndrome (GTS) is a sporadic or inherited complex neuropsychiatric disorder characterized by involuntary motor and vocal tics. There is comorbidity with disorders like obsessive compulsive disorder and attention deficit hyperactivity disorder. Until now linkage analysis has pointed to a number of chromosomal locations, but has failed to identify a clear candidate gene(s). We have investigated a GTS family with a complex chromosomal insertion/translocation involving chromosomes 2 and 7. The affected father [46,XY,inv(2) (p23q22),ins(7;2) (q35-q36;p21p23)] and two affected children [46,XX,der(7)ins(7;2)(q35-q36;p21p23) and 46,XY,der(7)ins(7;2)(q35-q36;p213p23)] share a chromosome 2p21-p23 insertion on chromosome 7q35-q36, thereby interrupting the contactin-associated protein 2 gene (CNTNAP2). This gene encodes a membrane protein located in a specific compartment at the nodes of Ranvier of axons. We hypothesize that disruption or decreased expression of CNTNAP2 could lead to a disturbed distribution of the K(+) channels in the nervous system, thereby influencing conduction and/or repolarization of action potentials, causing unwanted actions or movements in GTS.     

Longitudinal variance-components analysis of the Framingham Heart Study data

The Framingham Heart Study offspring cohort, a complex data set with irregularly spaced longitudinal phenotype data, was made available as part of Genetic Analysis Workshop 13. To allow an analysis of all of the data simultaneously, a mixed-model- based random-regression (RR) approach was used. The RR accounted for the variation in genetic effects (including marker-specific quantitative trait locus (QTL) effects) across time by fitting polynomials of age. The use of a mixed model allowed both fixed (such as sex) and random (such as familial environment) effects to be accounted for appropriately. Using this method we performed a QTL analysis of all of the available adult phenotype data (26,106 phenotypic records). In addition to RR, conventional univariate variance component techniques were applied. The traits of interest were BMI, HDLC, total cholesterol, and height. The longitudinal method allowed the characterization of the change in QTL effects with aging. A QTL affecting BMI was shown to act mainly at early ages.