From Fruit Flies to Barnacles, Histamine Is the Neurotransmitter of Arthropod Photoreceptors

Photoreceptor synapses of both vertebrate and invertebrate eyes are unconventional. These synapses release transmitter continuously yet never fatigue, and they transmit tiny presynaptic signals faithfully, often over a wide intensity range. Insight into these processes may now come with the identification of histamine as the neurotransmitter used by the photoreceptors of arthropod eyes. This minireview calls attention to peculiarities of arthropod photoreceptor synapses, reviews the evidence that histamine is the transmitter, and points out what we know of how histaminergic transmission is adapted to photoreceptor function

Attitudes and Preferences of ESL Students to Error Correction

This article presents the findings of a survey of ESL students' attitudes toward and preferences for the correction of spoken errors by native speaker friends. The 418 subjects reported generally positive attitudes toward error correction, and claimed to prefer even more correction than their friends did. They saw correcting errors as facilitating--even being necessary--for the improvement of their oral English

Error Correction in Native-Nonnative Conversation

The purpose of this paper is to report the results of an investigation into how native speakers (NSs) of English in social settings correct the errors committed by their friends who are nonnative speakers (NNSs) of English. While there are a number of studies which describe error correction in the second/foreign language classroom (e.g., Allwright 1975; Fanselow 1977; Holley and King 1971), little is known about what NSs do when their NNS friends commit errors. Gaskill (1980) studied sample conversations of one NNS with several NSs. He concluded that when, and if, NS correction occurs, it is usually modulated in form to show NS uncertainty. However, as Cathcart and Olsen (1976) noted, personalities involved in the interaction affect the amount and type of correction supplied. Since Gaskill had only one NNS as his source of data, his results may not be representative. The NSs in our data used two strategies tocorrect NNS errors: on-record corrections off-record corrections. After describing the subjects and the methods used in collecting the data, we discuss in detail these two strategies. We also present, by way of contrast, several noncorrective discourse strategies which NSs used in order to clear up conversational difficulties. A model of error correction is proposed, which shows that most NS error corrections were given at transition points and not as interruptions. The paper concludes with implications of the results for the classroom and with suggestions for future research

Comparative sequence analysis and tissue localization of members of the SLC6 family of transporters in adult Drosophila melanogaster

SUMMARY The SLC6 family comprises proteins that move extracellular neurotransmitters, amino acids and osmolytes across the plasma membrane into the cytosol. In mammals, deletion of SLC6 family members has dramatic physiologic consequences, but in the model organism Drosophila melanogaster, little is known about this family of proteins. Therefore, in this study we carried out an initial analysis of 21 known or putative SLC6 family members from the Drosophila genome. Protein sequences from these genes segregated into either well-defined subfamilies, including the novel insect amino acid transporter subfamily, or into a group of weakly related sequences not affiliated with a recognized subfamily. Reverse transcription-polymerase chain reaction analysis and in situ hybridization showed that seven of these genes are expressed in the CNS. In situ hybridization revealed that two previously cloned SLC6 members, the serotonin and dopamine transporters, were localized to presumptive presynaptic neurons that previously immunolabelled for these transmitters. RNA for CG1732 (the putative GABA transporter) and CG15088 (a member of the novel insect amino acid transporter family) was localized in cells likely to be subtypes of glia, while RNA for CG5226, CG10804 (both members of the orphan neurotransmitter transporter subfamily) and CG5549 (a putative glycine transporter) were expressed broadly throughout the cellular cortex of the CNS. Eight of the 21 sequences were localized outside the CNS in the alimentary canal, Malpighian tubules and reproductive organs. Localization for six sequences was not found or not attempted in the adult fly. We used the Drosophila ortholog of the mammalian vesicular monoamine transporter 2, CG33528, to independently identify monoaminergic neurons in the adult fly. RNA for CG33528 was detected in a limited number of cells in the central brain and in a beaded stripe at the base of the photoreceptors in the position of glia, but not in the photoreceptors themselves. The SLC6 localization observations in conjunction with likely substrates based on phylogenetic inferences are a first step in defining the role of Na/Cl-dependent transporters in Drosophila physiology

Uptake of Precursor and Synthesis of Transmitter in a Histaminergic Photoreceptor

As a first step in understanding how the supply of the neurotransmitter histamine is maintained in a photoreceptor, we followed the uptake and metabolism of the immediate precursor of histamine, histidine.

Using serum CA125 to assess the activity of potential cytostatic agents in ovarian cancer

Objective: New strategies are required to rapidly identify novel cytostatic agents before embarking on large randomized trials. This study investigates whether a change in rate of rise (slope) of serum CA125 from before to after starting a novel agent could be used to identify cytostatic agents. Tamoxifen was used to validate this hypothesis. Methods: Asymptomatic patients with relapsed ovarian cancer who had responded to chemotherapy were enrolled and had CA125 measurements taken every 4 weeks, then more frequently when rising. Once levels reached 4 times the upper limit of normal or nadir, they started continuous tamoxifen 20 mg daily, as well as fortnightly CA125 measurements until symptomatic progression. Because of the potentially nonlinear relationship of CA125 over time, it was felt that to enable normal approximations to be utilized a natural logarithmic standard transformation [ln(CA125)] was the most suitable to improve linearity above the common logarithmic transformation to base 10. Results: From 235 recruited patients, 81 started tamoxifen and had at least 4 CA125 measurements taken before and 4 CA125 measurements taken after starting tamoxifen, respectively. The mean regression slopes from using at least 4 1n(CA125) measurements immediately before and after starting tamoxifen were 0I0149 and 0I0093 [ln(CA125)/d], respectively. This difference is statistically significant, P = 0I001. Therefore, in a future trial with a novel agent, at least as effective as tamoxifen, using this effect size, the number of evaluable patients needed, at significance level of 5% and power of 80%, is 56. Conclusions: Further validation of this methodology is required, but there is potential to use comparison of mean regression slopes of ln(CA125) as an interim analysis measure of efficacy for novel cytostatic agents in relapsed ovarian cancer.Peer reviewedFinal Accepted Versio

Selective, Activity-Dependent Uptake of Histamine into an Arthropod Photoreceptor

The synapses made by many arthropod photoreceptors are disinhibitory and use histamine as their transmitter. Because decreases and not increases in the cleft concentration of transmitter constitute the important event at these synapses, a transporter to clear the cleft of histamine would seem particularly crucial to signal transfer. We report here tha

Recommendations for Clinical CYP2C9 Genotyping Allele Selection: A Joint Recommendation of the Association for Molecular Pathology and College of American Pathologists

The goals of the Association for Molecular Pathology Pharmacogenomics (PGx) Working Group of the Association for Molecular Pathology Clinical Practice Committee are to define the key attributes of PGx alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document provides recommendations for a minimum panel of variant alleles (Tier 1) and an extended panel of variant alleles (Tier 2) that will aid clinical laboratories when designing assays for CYP2C9 testing. The Working Group considered the functional impact of the variants, allele frequencies in different populations and ethnicities, the availability of reference materials, and other technical considerations for PGx testing when developing these recommendations. Our goal is to promote standardization of testing PGx genes and alleles across clinical laboratories. These recommendations are not to be interpreted as restrictive but to provide a reference guide. The current document will focus on CYP2C9 testing that can be applied to all CYP2C9-related medications. A separate recommendation on warfarin PGx testing is being developed to include recommendations on CYP2C9 alleles and additional warfarin sensitivity–associated genes and alleles

Impact of the Mt. Pinatubo volcaniceruption on the lower ionosphere andatmospheric waves over Central Europe

The very strong volcanic eruption of Mt. Pinatubo in June 1991 directly affected the troposphere and lower and middle stratosphere. Here we look at its effects in the mesopause region as revealed by the radio wave absorption measurements in the lower ionosphere over Central Europe and inferred planetary and gravity wave activity. The gravity wave activity inferred from the nighttime LF radio wave absorption displays an evident enhancement for waves of periods of about 2-3 h coinciding with regional measurements of the optical depth of (volcanic) aerosols, while there is no detectable effect for short period waves (T < 1 h). There is no detectable effect in the planetary wave activity inferred from the daytime HF radio wave absorption. As for the absorption itself, the results on the impact of the Mt. Pinatubo eruption do not provide an observable effect

The P2Y12 Receptor Antagonist Ticagrelor Reduces Lysosomal pH and Autofluorescence in Retinal Pigmented Epithelial Cells From the ABCA4-/- Mouse Model of Retinal Degeneration

The accumulation of partially degraded lipid waste in lysosomal-related organelles may contribute to pathology in many aging diseases. The presence of these lipofuscin granules is particularly evident in the autofluorescent lysosome-associated organelles of the retinal pigmented epithelial (RPE) cells, and may be related to early stages of age-related macular degeneration. While lysosomal enzymes degrade material optimally at acidic pH levels, lysosomal pH is elevated in RPE cells from the ABCA4-/- mouse model of Stargardt\u27s disease, an early onset retinal degeneration. Lowering lysosomal pH through cAMP-dependent pathways decreases accumulation of autofluorescent material in RPE cells in vitro, but identification of an appropriate receptor is crucial for manipulating this pathway in vivo. As the P2Y12 receptor for ADP is coupled to the inhibitory Gi protein, we asked whether blocking the P2Y12 receptor with ticagrelor could restore lysosomal acidity and reduce autofluorescence in compromised RPE cells from ABCA4-/- mice. Oral delivery of ticagrelor giving rise to clinically relevant exposure lowered lysosomal pH in these RPE cells. Ticagrelor also partially reduced autofluorescence in the RPE cells of ABCA4-/- mice. In vitro studies in ARPE-19 cells using more specific antagonists AR-C69931 and AR-C66096 confirmed the importance of the P2Y12 receptor for lowering lysosomal pH and reducing autofluorescence. These observations identify P2Y12 receptor blockade as a potential target to lower lysosomal pH and clear lysosomal waste in RPE cells. © 2018 Lu, Gómez, Lim, Guha, O\u27Brien-Jenkins, Coffey, Campagno, McCaughey, Laties, Carlsson and Mitchell