Genomic stability over 9 years of an isoniazid resistant Mycobacterium tuberculosis outbreak strain in Sweden

In molecular epidemiological studies of drug resistant Mycobacterium tuberculosis (TB) in Sweden a large outbreak of an isoniazid resistant strain was identified, involving 115 patients, mainly from the Horn of Africa. During the outbreak period, the genomic pattern of the outbreak strain has stayed virtually unchanged with regard to drug resistance, IS6110 restriction fragment length polymorphism and spoligotyping patterns. Here we present the complete genome sequence analyses of the index isolate and two isolates sampled nine years after the index case as well as experimental data on the virulence of this outbreak strain. Even though the strain has been present in the community for nine years and passaged between patients at least five times in-between the isolates, we only found four single nucleotide polymorphisms in one of the later isolates and a small (4 amino acids) deletion in the other compared to the index isolate. In contrast to many other evolutionarily successful outbreak lineages (e.g. the Beijing lineage) this outbreak strain appears to be genetically very stable yet evolutionarily successful in a low endemic country such as Sweden. These findings further illustrate that the rate of genomic variation in TB can be highly strain dependent, something that can have important implications for epidemiological studies as well as development of resistance.     

Effective Connectivity of Depth-Structure–Selective Patches in the Lateral Bank of the Macaque Intraparietal Sulcus

Extrastriate cortical areas are frequently composed of subpopulations of neurons encoding specific features or stimuli, such as color, disparity, or faces, and patches of neurons encoding similar stimulus properties are typically embedded in interconnected networks, such as the attention or face-processing network. The goal of the current study was to examine the effective connectivity of subsectors of neurons in the same cortical area with highly similar neuronal response properties. We first recorded single- and multi-unit activity to identify two neuronal patches in the anterior part of the macaque intraparietal sulcus (IPS) showing the same depth structure selectivity and then employed electrical microstimulation during functional magnetic resonance imaging in these patches to determine the effective connectivity of these patches. The two IPS subsectors we identified—with the same neuronal response properties and in some cases separated by only 3 mm—were effectively connected to remarkably distinct cortical networks in both dorsal and ventral stream in three macaques. Conversely, the differences in effective connectivity could account for the known visual-to-motor gradient within the anterior IPS. These results clarify the role of the anterior IPS as a pivotal brain region where dorsal and ventral visual stream interact during object analysis. Thus, in addition to the anatomical connectivity of cortical areas and the properties of individual neurons in these areas, the effective connectivity provides novel key insights into the widespread functional networks that support behavior.     

<Emphasis Type="Italic">Strychnos jacarepiensis</Emphasis>, a new species of Loganiaceae from Brazil

Strychnos jacarepiensis E. A. Manoel & E. F. Guim. is described and illustrated as a new species from Rio de Janeiro state, Brazil. It differs from S. gardneri by the terminal inflorescence and shorter corolla tube, and from S. brasiliensis by the connate and amplexicaul interpetiolar stipule, velutinous calyx lobes, villous filaments and discoid seeds.     

Extracellular low pH affects circadian rhythm expression in human primary fibroblasts

Circadian rhythm is a fundamental biological system involved in the regulation of various physiological functions. However, little is known about a nature or function of circadian clock in human primary cells. In the present study, we have applied in vitro real time circadian rhythm monitoring to study human clock properties using primary skin fibroblasts. Among factors that affect human physiology, slightly lower extracellular pH was chosen to test its effects on circadian rhythm expression. We established human primary fibroblast cultures obtained from three healthy subjects, stably delivered a circadian reporter gene Bmal1-luciferase, and recorded circadian rhythms in the culture medium at pH 7.2 and 6.7. At pH 7.2, robust and sustained circadian rhythms were observed with average period length 24.47 ± 0.03 h. Such rhythms were also found at pH 6.7; however, period length was significantly shortened to 22.60 ± 0.20, amplitude was increased, and damping rate was decreased. The effect of exposure to low pH on the period length was reversible. The shortened period was unlikely caused by factors affecting cell viability because cell morphology and MTT assay showed no significant difference between the two conditions. In summary, our results showed that the circadian rhythm expression is affected at pH 6.7 in human primary fibroblasts without affecting cell viability.     

S-Adenosylhomocysteine hydrolase of the protozoan parasite Trichomonas vaginalis: potent inhibitory activity of 9-(2-deoxy-2-fluoro-β,D-arabinofuranosyl)adenine

In the present study, we carried out a structure-activity analysis in Trichomonas vaginalis of a series of adenosine and uridine analogues. The most potent compounds were found to be 2' and 3' modified adenosine analogues some of which are potent inhibitors of S-adenosylhomocysteine hydrolase. The 9-(2-deoxy-2-fluoro-β,D-arabinofuranosyl)adenine compound was more potent than metronidazole, a current FDA approved and commonly prescribed drug for treatment of trichomoniasis. Its IC(50) was 0.09 μM compared to 0.72 μM for metronidazole.     

An in vitro approach to the study of target organ toxicity of drugs and chemicals

Summary A major goal of our laboratory has been the development of primary culture systems that retain differentiated fucntions and responses characteristic of intact tissues in vivo. Specifically, we have developed cellular models of primary cultures of rat heart, liver, and kidney cells to explore the mechanisms by which drugs or chemicals may be toxic to key organs of the body and to develop new techniques by which xenobiotics may be evaluated or identified as potential toxicants to living systems. The purpose of this paper is to describe our rationale and approach to the study of target organ toxicology with in vitro cellular systems.     

Bread Iodine Content and Thyroid Radioiodine Uptake: A Tale of Two Cities

The iodine content of bread consumed in the Bronx, New York, was found to be significantly lower than that of bread consumed in Columbia, Missouri. This difference in dietary intake of iodine could account for the lowered range of normal values for 24-hour ¹³¹I uptake tests in Columbia, and the persistence of the same normal range for this test over the past 28 years in the Bronx. A population with high iodine intake requires higher doses of radioactive iodine in the diagnosis and treatment of thyroid disease. Questions are raised regarding the relationship of high iodine intake to the risk of developing thyrotoxicosis.     

The effect of an alternative food supply on the relationship between two Typhlodromus species and Panonychus ulmi (Koch) (Acarina)

Using seedling plants in an insectary, populations were recorded of two species of Typhlodromus (Phytoseiidae) when provided with known numbers of Panonychus ulmi (Koch) (Tetranychidae) and/or large numbers of Aculus fockeui (Nal.) (Eriophyidae). T. pyri Scheut. and T. finlandicus (Oudms.) both maintained P. ulmi at a low level compared with populations where Typhlodromus was not present, and whether or not A. fockeui was also available. Both species of Typhlodromus increased more rapidly when provided with A. fockeui as well as P. ulmi, and under these conditions T. pyri reduced P. ulmi to a lower level than where A. fockeui was not provided.

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Zusammenfassung Der Versuch sollte zeigen, ob die Raubmilbe Typhlodromus spp. (Phytoseiidae) die Spinnmilbe Panonychus ulmi (Koch) (Tetranychidae) weiter niederhalten könnte, wenn gleichzeitig eine andere günstige Beute angeboten würde. Es wurden getopfte Prunus-Sämlinge in einem Gewächshaus benutzt, die zur Hälfte mit einer großen Anzahl von Aculus fockeui (Nal.) (Eriophyidae) infiziert wurden, bevor bekannte Anzahlen von P. ulmi und Typhlodromus pyri Scheut. oder T. finlandicus (Oudms.) auf ihnen angesetzt wurden. Während eines Zeitraumes von 8 Wochen wurden in annähernd wöchentlichen Abständen einzelne, als Wiederholungen angesetzte Pflanzen jeder Versuchsvariante entnommen und ihre Milbenpopulationen ausgezählt. Bei Abwesenheit der Raubmilben stieg die P. ulmi-Population schneller auf Pflanzen an, die von A. fockeui frei, als auf solchen, auf denen sie vorhanden waren. Sowohl T. pyri wie T. finlandicus hielten P. ulmi auf einem vergleichsweise niedrigen Niveau, gleichgültig ob A. fockeui gleichfalls vorhanden war oder nicht. Beide Typhlodromus-Arten vermehrten sich rascher, wenn ihnen neben P. ulmi zusätzlich A. fockeui zur Verfügung stand, und unter diesen Bedingungen reduzierte T. pyri die P. ulmi-Population auf ein niedrigeres Niveau als bei Abwesenheit von A. fockeui. Diese Ergebnisse zeigen, daß die Gegenwart von A. fockeui die Bekämpfung von P. ulmi durch Typhlodromus spp. nicht beeinträchtigt, daß sie aber eine günstige Beute darstellt und eine erhöhte Vermehrungsrate der Raubmilben bewirkt.