Evaluation of antigens for the serodiagnosis of kala-azar and oriental sores by means of the indirect immunofluorescence antibody test (IFAT)

Antigens and corresponding sera were collected from travellers with leishmaniasis returning to Germany from different endemic areas of the old world. The antigenicity of these Leishmania strains, which were maintained in Syrian hamsters, was compared by indirect immunofluorescence (IFAT). Antigenicity was demonstrated by antibody titres in 18 sera from 11 patients. The amastigotic stages of nine strains of Leishmania donovani and four strains of Leishmania tropica were compared with each other and with the culture forms of insect flagellates (Strigomonas oncopelti and Leptomonas ctenocephali). Eighteen sera from 11 patients were available for antibody determination with these antigens. The maximal antibody titres in a single serum varied considerably depending on which antigen was used for the test. High antibody levels could only be maintained when Leishmania donovani was employed as the antigen, but considerable differences also occurred between the different strains of this species. The other antigens were weaker. No differences in antigenicity between amastigotes and promastigotes of the same strain were observed. It is important to select suitable antigens. Low titres may be of doubtful specificity and are a poor baseline for the fall in titre which is an essential index of effective treatment.Wir sammelten Parasiten und Seren von Reisenden, die aus verschiedenen endemischen Gebieten der Alten Welt mit einer Leishmaniasis nach Deutschland zurückkehrten. Die Antigenaktivitäten der isolierten und fortlaufend in Goldhamstern gehaltenenLeishmania-Stämme wurden im indirekten Immunofluoreszenztest (IFAT) verglichen. Die Antigenität wurde an Hand von Antikörpertitern in 18 Serumproben von 11 Patienten bewiesen. Neun Stämme desLeishmania donovani-Komplexes und vierLeishmania tropica-Isolate wurden in ihrem amastigoten Stadium miteinander verglichen. Hinzu kamen zwei Insekten-Flagellaten als Kulturformen:Strigomonas oncopelti undLeptomonas ctenocephali. 18 Serumproben von 11 Patienten standen für die Antikörperbestimmung mit diesen Antigenen zur Verfügung. Die maximalen Titerhöhen variierten in ein- und derselben antiserumprobe zum Teil erheblich, je nachdem, welches Antigen für den Test benutzt wurde. Hohe Antikörpertiter konnten nur erhalten werden, wennLeishmania donovani als Antigen vorlag, es ergaben sich aber auch zwischen den einzelnen Stämmen dieser Leishmaniaart erhebliche Unterschiede in der Antigenaktivität. Antigene anderer Art erwiesen sich als wenig wirksam. Zwischen amastigoten und promastigoten Entwicklungsformen einesLeishmania donovani-Stammes konnten keine Unterschiede in der Antigenaktivität erkannt werden. Für den Nachweis möglichst hoher Antikörpertiter im IFAT ist die Auswahl geeigneter Antigene von ausschlaggebender Bedeutung. Niedrige Titer erschweren deren Beurteilung als spezifisch und sind eine schlechte Ausgangsposition für die Beobachtung des obligatorischen Titerabfalles nach erfolgreicher Therapie

The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

Background: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT. Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine. Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists. Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum. Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions. Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal

AMSA Conference Indigenous Workshop Summary

This report summarises a two-day Indigenous Workshop at the 2022 Australian Marine Sciences Association Conference. The workshop was the seventh to be supported by the National Environmental Science Program and the most significant to date in terms of Indigenous leadership and attendance. Indigenous participants from 45 language groups joined others from government, research and non-profit agencies. Indigenous organisations expressed a clear desire to work with government and research agencies to enable effective co-development of research, and to establish a nationally coordinated approach to Indigenous-led research and monitoring. The two-day Indigenous workshop brought together Indigenous leaders and community members from across the nation. This was a rare occasion for Indigenous Australians to come together and provide input into two important focal areas. 1. Collaborate and strategise on the research priorities, opportunities and constraints for Indigenous participation and leadership in environmental research in Australia’s marine and coastal regions. 2. Discuss the need for a National Indigenous Environmental Research Network (NIERN)

Developmental triclosan exposure decreases maternal, fetal, and early neonatal thyroxine: A dynamic and kinetic evaluation of a putative mode-of-action

This work tests the mode-of-action (MOA) hypothesis that maternal and developmental triclosan (TCS) exposure decreases circulating thyroxine (T4) concentrations via up-regulation of hepatic catabolism and elimination of T4. Time-pregnant Long-Evans rats received TCS po (0–300 mg/kg/day) from gestational day (GD) 6 through postnatal day (PND) 21. Serum and liver were collected from dams (GD20, PND22) and offspring (GD20, PND4, PND14, PND21). Serum T4, triiodothyronine (T3), and thyroid stimulating hormone (TSH) concentrations were measured by radioimmunoassay. Ethoxy-O-deethylase (EROD), pentoxyresorufin-O-depentylase (PROD) and uridine diphosphate glucuronyltransferase (UGT) enzyme activities were measured in liver microsomes. Custom Taqman® qPCR arrays were employed to measure hepatic mRNA expression of select cytochrome P450s, UGTs, sulfotransferases, transporters, and thyroid-hormone responsive genes. TCS was quantified by LC/MS/MS in serum and liver. Serum T4 decreased approximately 30% in GD20 dams and fetuses, PND4 pups and PND22 dams (300 mg/kg/day). Hepatic PROD activity increased 2- to 3-fold in PND4 pups and PND22 dams, and UGT activity was 1.5-fold higher in PND22 dams only (300 mg/kg/day). Minor up-regulation of Cyp2b and Cyp3a expression in dams was consistent with hypothesized activation of the constitutive androstane and/or pregnane X receptor. T4 reductions of 30% for dams and GD20 and PND4 offspring with concomitant increases in PROD (PND4 neonates and PND22 dams) and UGT activity (PND22 dams) suggest that up-regulated hepatic catabolism may contribute to TCS–induced hypothyroxinemia during development. Serum and liver TCS concentrations demonstrated greater fetal than postnatal internal exposure, consistent with the lack of T4 changes in PND14 and PND21 offspring. These data support the MOA hypothesis that TCS exposure leads to hypothyroxinemia via increased hepatic catabolism; however, the minor effects on thyroid hormone metabolism may reflect the low efficacy of TCS as thyroid hormone disruptor or highlight the possibility that other MOAs may also contribute to the observed maternal and early neonatal hypothyroxinemia

Bacterial microevolution and the Pangenome

The comparison of multiple genome sequences sampled from a bacterial population reveals considerable diversity in both the core and the accessory parts of the pangenome. This diversity can be analysed in terms of microevolutionary events that took place since the genomes shared a common ancestor, especially deletion, duplication, and recombination. We review the basic modelling ingredients used implicitly or explicitly when performing such a pangenome analysis. In particular, we describe a basic neutral phylogenetic framework of bacterial pangenome microevolution, which is not incompatible with evaluating the role of natural selection. We survey the different ways in which pangenome data is summarised in order to be included in microevolutionary models, as well as the main methodological approaches that have been proposed to reconstruct pangenome microevolutionary history

Seasonal and Altitudinal Changes in Population Density of 20 Species of Drosophila in Chamundi Hill

A year long study was conducted to analyze the altitudinal and seasonal variation in a population of Drosophila (Diptera: Drosophilidae) on Chamundi hill of Mysore, Karnataka State, India. A total of 16,671 Drosophila flies belonging to 20 species of 4 subgenera were collected at altitudes of 680 m, 780 m, 880 m and 980 m. The subgenus Sophophora was predominant with 14 species and the subgenus Drosilopha was least represented with only a single species. Cluster analysis and constancy methods were used to analyze the species occurrence qualitatively. Altitudinal changes in the population density, and relative abundance of the different species at different seasons were also studied. The diversity of the Drosophila community was assessed by applying the Simpson and Berger-Parker indices. At 680 m the Simpson Index was low at 0.129 and the Berger- Parker index was high at 1.1 at 980 m. Linear regression showed that the Drosophila community was positively correlated with rainfall but not elevation, Furthermore the density of Drosophila changed significantly in different seasons (F = 11.20, df 2, 9; P<0.004). The distributional pattern of a species or related group of species was uneven in space and time. D. malerkotliana and D. nasuta were found at all altitudes and can be considered as dominant species

Avoidance of cigarette pack health warnings among regular cigarette smokers

Background: Previous research with adults and adolescents indicates that plain cigarette packs increase visual attention to health warnings among non-smokers and non-regular smokers, but not among regular smokers. This may be because regular smokers: (1) are familiar with the health warnings, (2) preferentially attend to branding, or (3) actively avoid health warnings. We sought to distinguish between these explanations using eye-tracking technology. Method: A convenience sample of 30 adult dependent smokers participated in an eye-tracking study. Participants viewed branded, plain and blank packs of cigarettes with familiar and unfamiliar health warnings. The number of fixations to health warnings and branding on the different pack types were recorded. Results: Analysis of variance indicated that regular smokers were biased towards fixating the branding rather than the health warning on all three pack types. This bias was smaller, but still evident, for blank packs, where smokers preferentially attended the blank region over the health warnings. Time-course analysis showed that for branded and plain packs, attention was preferentially directed to the branding location for the entire 10. s of the stimulus presentation, while for blank packs this occurred for the last 8. s of the stimulus presentation. Familiarity with health warnings had no effect on eye gaze location. Conclusion: Smokers actively avoid cigarette pack health warnings, and this remains the case even in the absence of salient branding information. Smokers may have learned to divert their attention away from cigarette pack health warnings. These findings have implications for cigarette packaging and health warning policy

An efficient algorithm for the stochastic simulation of the hybridization of DNA to microarrays

<p>Abstract</p> <p>Background</p> <p>Although oligonucleotide microarray technology is ubiquitous in genomic research, reproducibility and standardization of expression measurements still concern many researchers. Cross-hybridization between microarray probes and non-target ssDNA has been implicated as a primary factor in sensitivity and selectivity loss. Since hybridization is a chemical process, it may be modeled at a population-level using a combination of material balance equations and thermodynamics. However, the hybridization reaction network may be exceptionally large for commercial arrays, which often possess at least one reporter per transcript. Quantification of the kinetics and equilibrium of exceptionally large chemical systems of this type is numerically infeasible with customary approaches.</p> <p>Results</p> <p>In this paper, we present a robust and computationally efficient algorithm for the simulation of hybridization processes underlying microarray assays. Our method may be utilized to identify the extent to which nucleic acid targets (e.g. cDNA) will cross-hybridize with probes, and by extension, characterize probe robustnessusing the information specified by MAGE-TAB. Using this algorithm, we characterize cross-hybridization in a modified commercial microarray assay.</p> <p>Conclusions</p> <p>By integrating stochastic simulation with thermodynamic prediction tools for DNA hybridization, one may robustly and rapidly characterize of the selectivity of a proposed microarray design at the probe and "system" levels. Our code is available at <url>http://www.laurenzi.net</url>.</p