Long-Chain Acyl-Carnitines Interfere with Mitochondrial ATP Production Leading to Cardiac Dysfunction in Zebrafish

In the human heart, the energy supplied by the production of ATP is predominately accomplished by ß-oxidation in mitochondria, using fatty acids (FAs) as the primary fuel. Long-chain acylcarnitines (LCACs) are intermediate forms of FA transport that are essential for FA delivery from the cytosol into mitochondria. Here, we analyzed the impact of the LCACs C18 and C18:1 on mitochondrial function and, subsequently, on heart functionality in the in vivo vertebrate model system of zebrafish (Danio rerio). Since LCACs are formed and metabolized in mitochondria, we assessed mitochondrial morphology, structure and density in C18- and C18:1-treated zebrafish and found no mitochondrial alterations compared to control-treated (short-chain acylcarnitine, C3) zebrafish embryos. However, mitochondrial function and subsequently ATP production was severely impaired in C18- and C18:1-treated zebrafish embryos. Furthermore, we found that C18 and C18:1 treatment of zebrafish embryos led to significantly impaired cardiac contractile function, accompanied by reduced heart rate and diminished atrial and ventricular fractional shortening, without interfering with cardiomyocyte differentiation, specification and growth. In summary, our findings provide insights into the direct role of long-chain acylcarnitines on vertebrate heart function by interfering with regular mitochondrial function and thereby energy allocation in cardiomyocytes.     

Electrical transport properties of low-stage AsF5-intercalated graphite

The in-plane resistivity of stage 1 and stage 2 AsF₅-graphite intercalation compounds was measured using a contactless r.f. eddy current technique from 1.6 to 290 K. The magnetoresistance of a stage 1 compound was similarly measured from 4.2 K to 290 K. The low temperature stage 2 resistivity data show a well-defined intermediate T ² region in addition to the usual T high temperature region, in qualitative agreement with the Kukkonen theory and indicative of a small, elongated cylindrical Fermi surface. Stage 2 resistivity data also show, for the first time in a graphite-acceptor compound, an apparent low temperature phase transition at 21 K. Magnetoresistance data were used to determine a stage 1 carrier concentration of 9×10²⁰ holes cm^–3. Resistive anomalies were observed at 200 K and 220 K for stage 1 and stage 2 compounds, respectively.     

Tobacco industry litigation position on addiction: continued dependence on past views

This paper reviews the tobacco industry's litigation strategy for addressing the addiction issue through trial testimony by its experts, and opening and closing statements by its lawyers. Despite the fact that several companies now claim to accept, in varying degrees, the conclusions of the Surgeon General concerning tobacco addiction, the tobacco industry litigation strategy pertaining to addiction is essentially unchanged since that of the early 1980s when the issue emerged as crucial. The industry uses its experts and the process of cross-examination of plaintiff's experts to imply that the addictiveness of tobacco and nicotine are more comparable to substances such as caffeine, chocolate, and even milk, than to heroin, cocaine and alcohol. Furthermore, the tobacco industry contends that the definition of addiction has now become so broadened as to include carrots and caffeine and hence that any concurrence that smoking is addictive, does not imply that cigarettes are addictive to the standards that drugs such as heroin and cocaine are addictive. Finally, the industry has continuously asserted that tobacco users assumed the risks of tobacco since they understood that quitting could be difficult when they began to use, and moreover, that the main barrier to cessation is lack of desire or motivation to quit and not physical addiction. These positions have been maintained through the 2004-2005 US Government litigation that was ongoing as the time of this writing.     

Reducing tobacco addiction through tobacco product regulation

Tobacco product regulation has the potential to help reduce tobacco attributable disease by reducing the toxicity of these products and by reducing the prevalence of tobacco use and addiction.     

Usefulness of screening investigations in neurofibromatosis type 1. A study of 152 patients

OBJECTIVE: To evaluate the usefulness of screening investigations in patients with neurofibromatosis type 1 (NF1). DESIGN: Clinical and screening data were retrospectively collected from a case series of patients with NF1. Screening investigations included an opthalmologic consultation, chest x-ray film, abdominal ultrasonography, cerebral imaging, and analysis of urinary catecholamine levels. Clinical features and complications of patients with NF1 were compared with those of the Neurofibromatoses Institute Clinical Research Program and of the Southeast Wales study patients. SETTING: Ambulatory care in a referral center. PATIENTS: Between 1988 and 1992, 152 patients classified as having NF1 according to the criteria of the National Institutes of Health Consensus Development Conference Statement were studied. MAIN OUTCOME MEASURE: Complications requiring therapeutic action detected using screening investigations vs clinical examination. RESULTS: Systemic chest x-ray films were taken of 134 patients, and intrathoracic nodules thought to be neurofibromas were discovered in 2 patients. Ninety-three asymptomatic patients had cerebral imaging performed, which showed optic pathway glioma in 12 patients. Abdominal ultrasonography was performed on 62 asymptomatic patients, results of which showed internal neurofibromas in 4 patients. In 2 of these patients, abdominal surgery was performed. Eighty-three patients without hypertension had 24-hour urinary specific catecholamine levels analyzed, which were within the normal range. Clinical features and complications were not different from other large clinical studies. Nearly 400 systematic investigations were performed without clinical orientation, detecting 21 abnormalities. In only 2 cases, these discoveries led to therapeutic action. On the other hand, 22 complications requiring treatment were detected by clinical examination. CONCLUSION: Clinical follow-up seems to be more beneficial than systematic investigations in patients with NF1.     

Die Entwicklung des virtuellen Speichers

Ohne Zusammenfassung     

Contactless technique for the measurement of electrical resistivity in anisotropic materials

Measurement of basal plane electrical resistivities in quasi-two-dimensional materials by conventional four-point bridge techniques is extremely difficult. In making measurements of room temperature basal plane resistivities in highly conducting highly anisotropic synthetic metals we have developed an rf inductive technique which is both simple to use and provides accurate results. At the frequency we employ (100 kHz) the method is appropriate for resistivities in the range 10 (-3)-10(-7)Omega cm. Samples are thin square plates 5 mm on a side. The system is calibrated by fitting data from a series of samples of known resistivity to semi-empirical formulae. The theoretical motivation leading to these expressions is discussed and extensive calibration data are presented. The advantages of rf techniques in general have already been discussed. Two advantages commend the particular technique we describe here. First, it is simple in design and easily constructed. Second, with careful calibration, highly accurate resistivity measurements can be made in a very straightforward manner.