Some characteristics and antibiotic resistance of anaerobic bacteria from the ceca and colons of pigs fed chlortetracycline-containing and unmedicated diets

Morphology and end product patterns were used to group 112 bacterial isolates from the ceca and colons of pigs fed unmedicated and chlortetracycline-containing diets. Most of the isolates (68%) were resistant to chlortetracycline (greater than 4 micrograms/ml). Chlortetracycline resistance was associated with all groups of anaerobic and facultative bacteria.     

Evidence for an elevated frequency of in vivo somatic cell mutations in ataxia telangiectasia.

Somatic cell mutation frequency in vivo was measured in individuals with high cancer risk who were from ataxia telangiectasia (A-T) families. The assay for somatic mutation measures the frequency of variant erythrocytes which are progeny of erythroid precursor cells with mutations that result in a loss of gene expression at the polymorphic glycophorin A (GPA) locus. Samples from 14 of 15 A-T homozygotes showed high frequencies of GPA gene expression-loss variant cells with normal expression of only one of the two alleles at the GPA locus (i.e., GPA hemizygous variant cells). The mean elevation of the frequency of hemizygous variant cells over those in normal controls and unaffected family members was 7-14-fold. A-T homozygotes also showed an increase in the frequency of cells in which one allele at the GPA locus had lost expression and in which the remaining allele was expressed at a homozygous level (i.e., GPA homozygous variant cells). Family members who are obligate A-T heterozygotes did not appear to have a significantly elevated frequency of GPA hemizygous or homozygous variant cells. These indications of elevated in vivo frequencies of variant erythrocytes in A-T homozygotes support a causal link between susceptibility to somatic mutation and susceptibility to cancer.     

Optocardiography: In vivo measurements of the insect cardiac activity with a new optical method

A new method allowing long-term in vivo evaluation of the insect cardiac activity is described. Comparison with other methods and experimental results indicate the advantages of the new method over classical techniques. The basic cardiac cycle and cardiac activity patterns as recorded by this method are shown. The independent cardiac activity of different chambers of the dorsal vessel of Schistocerca gregaria is demonstrated. A preliminary explanation of these events is given.     

Élaboration de nouveaux systèmes biodégradables électrogreffables pour stents endovasculaires métalliques

In this project concerning the development of new endovascular stents, which controlled the release of pharmacological molecules, we prepared biodegradable and biocompatible macromonomers of poly (lactic acid), with controlled molar mass (600 g/mol), having a double bond allowing afterward the electrografting on metallic stent. This biodegradable layer has for role to improve the interface between the metal and the degradable polymer matrix which will be later deposited on the stent to assure a good liberation of the active principle (DES). We tested the feasibility of the electrografting of this layer with PLA, its in vitro then in vivo degradation as well as the recolonisation of the stent by cells. The positive results obtained in this study are completely encouraging for the development of new DES.     

Pharmacological Characterization of an Antisense Knockdown Zebrafish Model of Dravet Syndrome: Inhibition of Epileptic Seizures by the Serotonin Agonist Fenfluramine

Dravet syndrome (DS) is one of the most pharmacoresistant and devastating forms of childhood epilepsy syndromes. Distinct de novo mutations in the SCN1A gene are responsible for over 80% of DS cases. While DS is largely resistant to treatment with existing anti-epileptic drugs, promising results have been obtained in clinical trials with human patients treated with the serotonin agonist fenfluramine as an add-on therapeutic. We developed a zebrafish model of DS using morpholino antisense oligomers (MOs) targeting scn1Lab, the zebrafish ortholog of SCN1A. Zebrafish larvae with an antisense knockdown of scn1Lab (scn1Lab morphants) were characterized by automated behavioral tracking and high-resolution video imaging, in addition to measuring brain activity through local field potential recordings. Our findings reveal that scn1Lab morphants display hyperactivity, convulsive seizure-like behavior, loss of posture, repetitive jerking and a myoclonic seizure-like pattern. The occurrence of spontaneous seizures was confirmed by local field potential recordings of the forebrain, measuring epileptiform discharges. Furthermore, we show that these larvae are remarkably sensitive to hyperthermia, similar to what has been described for mouse models of DS, as well as for human DS patients. Pharmacological evaluation revealed that sodium valproate and fenfluramine significantly reduce epileptiform discharges in scn1Lab morphants. Our findings for this zebrafish model of DS are in accordance with clinical data for human DS patients. To our knowledge, this is the first study demonstrating effective seizure inhibition of fenfluramine in an animal model of Dravet syndrome. Moreover, these results provide a basis for identifying novel analogs with improved activity and significantly milder or no side effects.     

Spatial‐Temporal Modeling of the Association between Air Pollution Exposure and Preterm Birth: Identifying Critical Windows of Exposure

Summary Exposure to high levels of air pollution during the pregnancy is associated with increased probability of preterm birth (PTB), a major cause of infant morbidity and mortality. New statistical methodology is required to specifically determine when a particular pollutant impacts the PTB outcome, to determine the role of different pollutants, and to characterize the spatial variability in these results. We develop a new Bayesian spatial model for PTB which identifies susceptible windows throughout the pregnancy jointly for multiple pollutants (PM_2.5 , ozone) while allowing these windows to vary continuously across space and time. We geo‐code vital record birth data from Texas (2002–2004) and link them with standard pollution monitoring data and a newly introduced EPA product of calibrated air pollution model output. We apply the fully spatial model to a region of 13 counties in eastern Texas consisting of highly urban as well as rural areas. Our results indicate significant signal in the first two trimesters of pregnancy with different pollutants leading to different critical windows. Introducing the spatial aspect uncovers critical windows previously unidentified when space is ignored. A proper inference procedure is introduced to correctly analyze these windows.