955 research outputs found

    The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons.

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    BACKGROUND: While developmental processes such as axon pathfinding and synapse formation have been characterized in detail, comparatively less is known of the intrinsic developmental mechanisms that regulate transcription of ion channel genes in embryonic neurons. Early decisions, including motoneuron axon targeting, are orchestrated by a cohort of transcription factors that act together in a combinatorial manner. These transcription factors include Even-skipped (Eve), islet and Lim3. The perdurance of these factors in late embryonic neurons is, however, indicative that they might also regulate additional aspects of neuron development, including the acquisition of electrical properties. RESULTS: To test the hypothesis that a combinatorial code transcription factor is also able to influence the acquisition of electrical properties in embryonic neurons we utilized the molecular genetics of Drosophila to manipulate the expression of Eve in identified motoneurons. We show that increasing expression of this transcription factor, in two Eve-positive motoneurons (aCC and RP2), is indeed sufficient to affect the electrical properties of these neurons in early first instar larvae. Specifically, we observed a decrease in both the fast K+ conductance (IKfast) and amplitude of quantal cholinergic synaptic input. We used charybdotoxin to pharmacologically separate the individual components of IKfast to show that increased Eve specifically down regulates the Slowpoke (a BK Ca2+-gated potassium channel), but not Shal, component of this current. Identification of target genes for Eve, using DNA adenine methyltransferase identification, revealed strong binding sites in slowpoke and nAcRalpha-96Aa (a nicotinic acetylcholine receptor subunit). Verification using real-time PCR shows that pan-neuronal expression of eve is sufficient to repress transcripts for both slo and nAcRalpha-96Aa. CONCLUSION: Taken together, our findings demonstrate, for the first time, that Eve is sufficient to regulate both voltage- and ligand-gated currents in motoneurons, extending its known repertoire of action beyond its already characterized role in axon guidance. Our data are also consistent with a common developmental program that utilizes a defined set of transcription factors to determine both morphological and functional neuronal properties

    Antidepressant medication use in Inflammatory Bowel Disease: a nationally representative population-based study.

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    BACKGROUND: Despite high rates of depression and anxiety, little is known about the use of antidepressants amongst individuals diagnosed with inflammatory bowel disease (IBD). AIMS: To evaluate temporal trends in the use of antidepressants; rates of antidepressant initiation and adherence of antidepressant use to international guidelines amongst individuals with IBD. METHODS: This is a study of 14,525 incident IBD cases from 2004 to 2016 compared with 58,027 controls matched 1:4 for age and sex from the Clinical Practice Research Datalink. After excluding tricyclic antidepressants, we performed a Cox regression analysis to determine the risk associated with antidepressant use and logistic regression analysis to determine risk associated with antidepressant undertreatment. RESULTS: Antidepressant use amongst individuals with IBD increased by 51% during the 12-year study period, who were 34% more likely to initiate antidepressants in the year after IBD diagnosis compared with controls (aHR:1.34, 95% CI 1.21-1.49). In those with IBD starting antidepressants, 67% received treatment lasting less than the duration recommended in international guidelines, of which 34% were treated for 1 month or less. 18-24 year olds were twice as likely to discontinue treatment within 1Β month compared with those aged 40-60Β years (aHR:2.03, 95% CI 1.40-2.95). Socioeconomic deprivation was also associated with early treatment discontinuation (aHR:1.40, 95% CI 1.07-1.83). CONCLUSIONS: In the year following IBD diagnosis individuals are significantly more likely to start antidepressants compared with controls, but treatment duration fell short of recommendations in the majority. Better integration of services may benefit individuals with IBD and psychiatric comorbidity

    The validation of a new comprehensive headache-specific quality of life questionnaire

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    BACKGROUND: Measuring quality of life (QOL) is an important means of assessing the impact of headache. The currently used QOL questionnaires are usually geared toward migraine and focus on a limited number of factors, thus they are not necessarily informative in other headache types. We report the psychometric properties of a new questionnaire, the Comprehensive Headache-related Quality of life Questionnaire (CHQQ) that may be more sensitive to the burden of headache. PATIENTS AND METHODS: A total of 202 patients suffering from migraine (n = 168) or tension-type headache (TTH) (n = 34) completed the CHQQ and SF-36, a generic QOL questionnaire. We assessed the reliability and validity of the CHQQ and its physical, mental and social dimensions. RESULTS: The questionnaire was easy to administer. Reliability was excellent with Cronbach's alpha being 0.913 for the whole instrument (0.814-0.832 for its dimensions). The dimensions and total score showed significant correlations with the patients' headache characteristics (criterion validity), and were also significantly correlated with the SF-36 domains (convergent validity). The total score and dimensions were significantly (p < 0.005) lower in the migraine group than in the TTH group (discriminative validity). CONCLUSION: In this study the new headache-specific QOL instrument showed adequate psychometric properties

    High resolution mapping of a novel late blight resistance gene Rpi-avll, from the wild Bolivian species Solanum avilesii

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    Both Mexico and South America are rich in Solanum species that might be valuable sources of resistance (R) genes to late blight (Phytophthora infestans). Here, we focus on an R gene present in the diploid Bolivian species S. avilesii. The genotype carrying the R gene was resistant to eight out of 10 Phytophthora isolates of various provenances. The identification of a resistant phenotype and the generation of a segregating population allowed the mapping of a single dominant R gene, Rpi-avl1, which is located in an R gene cluster on chromosome 11. This R gene cluster is considered as an R gene β€œhot spot”, containing R genes to at least five different pathogens. High resolution mapping of the Rpi-avl1 gene revealed a marker co-segregating in 3890 F1 individuals, which may be used for marker assisted selection in breeding programs and for further cloning of Rpi-avl

    Detection of Genetically Altered Copper Levels in Drosophila Tissues by Synchrotron X-Ray Fluorescence Microscopy

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    Tissue-specific manipulation of known copper transport genes in Drosophila tissues results in phenotypes that are presumably due to an alteration in copper levels in the targeted cells. However direct confirmation of this has to date been technically challenging. Measures of cellular copper content such as expression levels of copper-responsive genes or cuproenzyme activity levels, while useful, are indirect. First-generation copper-sensitive fluorophores show promise but currently lack the sensitivity required to detect subtle changes in copper levels. Moreover such techniques do not provide information regarding other relevant biometals such as zinc or iron. Traditional techniques for measuring elemental composition such as inductively coupled plasma mass spectroscopy are not sensitive enough for use with the small tissue amounts available in Drosophila research. Here we present synchrotron x-ray fluorescence microscopy analysis of two different Drosophila tissues, the larval wing imaginal disc, and sectioned adult fly heads and show that this technique can be used to detect changes in tissue copper levels caused by targeted manipulation of known copper homeostasis genes

    Model of Yield Response of Corn to Plant Population and Absorption of Solar Energy

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    Biomass yield of agronomic crops is influenced by a number of factors, including crop species, soil type, applied nutrients, water availability, and plant population. This article is focused on dependence of biomass yield (Mg haβˆ’1 and g plantβˆ’1) on plant population (plants mβˆ’2). Analysis includes data from the literature for three independent studies with the warm-season annual corn (Zea mays L.) grown in the United States. Data are analyzed with a simple exponential mathematical model which contains two parameters, viz. Ym (Mg haβˆ’1) for maximum yield at high plant population and c (m2 plantβˆ’1) for the population response coefficient. This analysis leads to a new parameter called characteristic plant population, xcβ€Š=β€Š1/c (plants mβˆ’2). The model is shown to describe the data rather well for the three field studies. In one study measurements were made of solar radiation at different positions in the plant canopy. The coefficient of absorption of solar energy was assumed to be the same as c and provided a physical basis for the exponential model. The three studies showed no definitive peak in yield with plant population, but generally exhibited asymptotic approach to maximum yield with increased plant population. Values of xc were very similar for the three field studies with the same crop species

    A comparison of the seasonal movements of tiger sharks and green turtles provides insight into their predator-prey relationship

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    During the reproductive season, sea turtles use a restricted area in the vicinity of their nesting beaches, making them vulnerable to predation. At Raine Island (Australia), the highest density green turtle Chelonia mydas rookery in the world, tiger sharks Galeocerdo cuvier have been observed to feed on green turtles, and it has been suggested that they may specialise on such air-breathing prey. However there is little information with which to examine this hypothesis. We compared the spatial and temporal components of movement behaviour of these two potentially interacting species in order to provide insight into the predator-prey relationship. Specifically, we tested the hypothesis that tiger shark movements are more concentrated at Raine Island during the green turtle nesting season than outside the turtle nesting season when turtles are not concentrated at Raine Island. Turtles showed area-restricted search behaviour around Raine Island for ~3&ndash;4 months during the nesting period (November&ndash;February). This was followed by direct movement (transit) to putative foraging grounds mostly in the Torres Straight where they switched to area-restricted search mode again, and remained resident for the remainder of the deployment (53&ndash;304 days). In contrast, tiger sharks displayed high spatial and temporal variation in movement behaviour which was not closely linked to the movement behaviour of green turtles or recognised turtle foraging grounds. On average, tiger sharks were concentrated around Raine Island throughout the year. While information on diet is required to determine whether tiger sharks are turtle specialists our results support the hypothesis that they target this predictable and plentiful prey during turtle nesting season, but they might not focus on this less predictable food source outside the nesting season

    Leading causes of certification for blindness and partial sight in England & Wales

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    Prevention of visual impairment is an international priority agreed at the World Health Assembly of 2002--yet many countries lack contemporary data about incidence and causes from which priorities for prevention, treatment and management can be identified
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