The control of gene expression is a fundamental process essential for correct development and to maintain homeostasis. Many post-transcriptional mechanisms exist to maintain the correct levels of ...each RNA transcript within the cell. Controlled and targeted cytoplasmic RNA degradation is one such mechanism with the 5'-3' exoribonuclease Pacman (XRN1) and the 3'-5' exoribonuclease Dis3L2 playing crucial roles. Loss of function mutations in either Pacman or Dis3L2 have been demonstrated to result in distinct phenotypes, and both have been implicated in human disease. One mechanism by which gene expression is controlled is through the function of miRNAs which have been shown to be crucial for the control of almost all cellular processes. Although the biogenesis and mechanisms of action of miRNAs have been comprehensively studied, the mechanisms regulating their own turnover are not well understood. Here we characterise the miRNA landscape in a natural developing tissue, the
wing imaginal disc, and assess the importance of Pacman and Dis3L2 on the abundance of miRNAs. We reveal a complex landscape of miRNA expression and show that whilst a null mutation in
has a minimal effect on the miRNA expression profile, loss of Pacman has a profound effect with a third of all detected miRNAs demonstrating Pacman sensitivity. We also reveal a role for Pacman in regulating the highly conserved
cluster (containing
and
) and present a genetic model outlining a positive feedback loop regulated by Pacman which enhances our understanding of the apoptotic phenotype observed in Pacman mutants.
Emergency contraception (EC) is an effective postcoital contraceptive method for reducing the risk of unwanted pregnancy after unprotected intercourse. The estimated effectiveness of EC is between 70 ...and 89% if taken within 72 h following intercourse. Most of the studies carried out in Spain are quantitative and from the perspective of health professionals. In this study, we intend to explore the knowledge of, attitudes towards and discourse regarding the use of EC in women aged 15 to 25 years.
Sample: A qualitative study including in-depth interviews with 19 women between 15 and 25 years of age was performed.
Participants were natives of Spain or of a Latin American country. Segmentation criteria: Participants had experience in the use of EC.
Participants were selected by health care informants and by the snowball technique among university students.
A thematic analysis was performed. Preliminary analyses were made during the course of the field work to adapt the script and to assess data saturation. A preliminary code tree was developed by two researchers, and the coding of the text was done with the Atlas.ti 5.0 software.
EC is perceived positively by women. They do not express issues with taking it, although some feel guilty. The reason for taking EC is to avoid unwanted pregnancy and abortion. Women also feel that EC should be used in moderation. False beliefs and misconceptions regarding EC are held: EC delivers an excess of hormones, induces abortion and causes severe side effects. Women mention that the health professionals who provide EC have moral beliefs. Women use it because of condom breakage associated with their first coital relations.
The results of this study have public health implications: The sexual-affective health education received by young people should incorporate clear information about the mechanism of action of the EC pill and its side effects together with empowerment strategies addressing guilt and moralistic messages. Programmes and training activities for health professionals must be designed to prevent the communication of inappropriate messages such as those that exaggerate the side effects of EC and those that promote fear and guilt, because they represent a barrier to the responsible use of this medication.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The dayside of HD 149026b is near the edge of detectability by the Spitzer Space Telescope. We report on 11 secondary-eclipse events at 3.6, 4.5, 3 x 5.8, 4 x 8.0, and 2 x 16 mu m plus three ...primary-transit events at 8.0 mu m. The eclipse depths from jointly fit models at each wavelength are 0.040% + or - 0.003% at 3.6 mu m, 0.034% + or - 0.006% at 4.5 mu m, 0.044% + or - 0.010% at 5.8 mu m, 0.052% + or - 0.006% at 8.0 mu m, and 0.085% + or - 0.032% at 16 mu m. Multiple observations at the longer wavelengths improved eclipse-depth signal-to-noise ratios by up to a factor of two and improved estimates of the planet-to-star radius ratio (R sub(p)/R sub(*) = 0.0518 + or - 0.0006). We also identify no significant deviations from a circular orbit and, using this model, report an improved period of 2.8758916 + or - 0.0000014 days. Chemical-equilibrium models find no indication of a temperature inversion in the dayside atmosphere of HD 149026b. Our best-fit model favors large amounts of CO and CO sub(2), moderate heat redistribution (f = 0.5), and a strongly enhanced metallicity. These analyses use BiLinearly-Interpolated Subpixel Sensitivity (BLISS) mapping, a new technique to model two position-dependent systematics (intrapixel variability and pixelation) by mapping the pixel surface at high resolution. BLISS mapping outperforms previous methods in both speed and goodness of fit. We also present an orthogonalization technique for linearly correlated parameters that accelerates the convergence of Markov chains that employ the Metropolis random walk sampler. The electronic supplement contains light-curve files.
Perisomatic inhibition of pyramidal neurons (PNs) coordinates cortical network activity during sensory processing, and this role is mainly attributed to parvalbumin-expressing basket cells (BCs). ...However, cannabinoid receptor type 1 (CB1)-expressing interneurons are also BCs, but the connectivity and function of these elusive but prominent neocortical inhibitory neurons are unclear. We find that their connectivity pattern is visual area specific. Persistently active CB1 signaling suppresses GABA release from CB1 BCs in the medial secondary visual cortex (V2M), but not in the primary visual cortex (V1). Accordingly, in vivo, tonic CB1 signaling is responsible for higher but less coordinated PN activity in the V2M than in the V1. These differential firing dynamics in the V1 and V2M can be captured by a computational network model that incorporates visual-area-specific properties. Our results indicate a differential CB1-mediated mechanism controlling PN activity, suggesting an alternative connectivity scheme of a specific GABAergic circuit in different cortical areas.
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•CB1+ basket cells exhibit visual-area-specific morphology and connectivity patterns•Tonic CB1 signaling underlies high pyramidal neurons (PN) activity in V2M but not V1•Tonic CB1 signaling differentially modulates PN-correlated activity in V1 and V2M•Numerical simulations capture specific CB1-dependent firing dynamics of V1 and V2M
Cannabinoid receptor type 1 (CB1) basket cells are prominent but elusive cortical interneurons, inhibiting the soma of principal neurons. Koukouli et al. show that CB1+ interneurons exhibit specific connectivity properties in distinct visual cortical areas and differently control the activity and coordination of primary (V1) and associative (V2M) visual areas.
•Resident microbes can influence insect immunity and their ability to acquire resources.•Microbes often directly supply nutrients, toxins, and other bio-active compounds.•Microbes can also modulate ...signaling pathways that influence resource use or defense.•Symbiont-provided traits may be conditioned by environmental factors.•Effects of infection potentially extend to trophic levels above and below.
The microbiota inhabiting insects influence a wide range of ecologically-important traits. In addition to their better-known roles in nutrient provisioning and degrading plant polymers, there is emerging evidence that microorganisms also aid herbivores in countering plant defenses. The latter can be mediated by enzymes that degrade plant allelochemicals or via the modulation of plant signaling pathways. Symbionts are also increasingly recognized to protect insects from attack by a wide range of natural enemies. Underlying mechanisms are poorly understood, but some microbes produce antimicrobials or toxins, while others modulate insect immune responses. Ecologically-relevant symbioses can exhibit dynamic variation in strength and specificity of conferred phenotypes, transfer key traits among unrelated insects, and have effects that extend to interacting players and beyond.
Participants completed three cued-switching tasks, responded to two category-fluency probes, two letter-fluency probes, and two probes to alternate between two targets. Correlations across the three ...cued-switching tasks were significant for both switching costs and mixing costs. The bilingual advantage hypothesis was tested both by forming language groups and treating bilingualism as a continuous variable. No bilingual advantages were observed. In verbal-fluency monolinguals generated more correct responses but the bilingual disadvantage on the category task was not reduced in the letter-fluency scores. The bilingual disadvantage was eliminated when the groups were matched on vocabulary size. The verbal-fluency measures obtained when participants alternated between targets weakly correlated with the switching-costs obtained in the cued-switching tasks.
▶ Cocaine-induced changes in the nucleus accumbens may result from homeostatic regulations. ▶ An early alteration is the appearance of silent synapses enriched in NR2B subunits. ▶ The increased ...NR2B-NMDA receptors may trigger a homeostatic decrease in membrane excitability. ▶ Newly formed silent synapses provide synaptic slots for recruitment of new AMPA receptors. ▶ The decreased membrane excitability may trigger a homeostatic recruitment of AMPA receptors.
Homeostatic response is an endowed self-correcting/maintaining property for living units, ranging from subcellular domains, single cells, and organs to the whole organism. Homeostatic responses maintain stable function through the ever-changing internal and external environments. In central neurons, several forms of homeostatic regulation have been identified, all of which tend to stabilize the functional output of neurons toward their prior “set-point.” Medium spiny neurons (MSNs) within the forebrain region the nucleus accumbens (NAc) play a central role in gating/regulating emotional and motivational behaviors including craving and seeking drugs of abuse. Exposure to highly salient stimuli such as cocaine administration not only acutely activates a certain population of NAc MSNs, but also induces long-lasting changes in these neurons. It is these long-lasting cellular alterations that are speculated to mediate the increasingly strong cocaine-craving and cocaine-seeking behaviors. Why do the potentially powerful homeostatic mechanisms fail to correct or compensate for these drug-induced maladaptations in neurons? Based on recent experimental results, this review proposes a hypothesis of homeostatic dysregulation induced by exposure to cocaine. Specifically, we hypothesize that exposure to cocaine generates false molecular signals which misleads the homeostatic regulation process, resulting in maladaptive changes in NAc MSNs. Thus, many molecular and cellular alterations observed in the addicted brain may indeed result from homeostatic dysregulation. This review is among the first to introduce the concept of homeostatic neuroplasticity to understanding the molecular and cellular maladaptations following exposure to drugs of abuse.
Energy performance of island tourism has been analyzed in the literature. However, tourist services tend to concentrate in tourist hubs, especially where mass tourism predominates (e.g., ...Mediterranean), and the energy metabolism of these systems has not yet been assessed. The present paper models and estimates the energy metabolism of tourist hubs in the Menorca Island (Spain) by integrating social, geographical and environmental methods. Mobility (both external and internal) and consumption of lodging services were characterized through surveys to users (tourists) and business managers. An environmental assessment evaluated CO2 emissions, and energy self-sufficiency potential was estimated via GIS data. The results indicate that, on average, a tourist consumes 4756MJ with associated emissions of 277kg of CO2 per stay (20 days on average). Of all the energy flows, external mobility contributes the most to total emissions (77%). For every day spent in a tourist hub, a tourist consumes between 29MJ and 93MJ in lodging services, consumption that could be 100% satisfied by photovoltaic systems, and these systems would result in positive effects for the island. Sustainable tourism management might focus on promoting environmentally friendly transportation, energy efficient practices, and environmental communication through ecolabeling.
•We modeled the entire energy metabolism of tourist hubs in islands.•Results showed that a tourist in Menorca consumes from 4000 to 6000MJ per trip.•External mobility (trip to the island) accounts for 77% of the total CO2 emissions.•Photovoltaic systems could provide enough power to achieve self-sufficiency.•Tourists at hotel hubs have higher energy consumption than other types of hubs.
A growing body of literature links events associated with the progression and severity of immunity and inflammatory disease with the composition of the tissue extracellular matrix as defined by the ...matrisome. One protein in the matrisome that is common to many inflammatory diseases is the large proteoglycan versican, whose varied function is achieved through multiple isoforms and post-translational modifications of glycosaminoglycan structures. In cancer, increased levels of versican are associated with immune cell phenotype, disease prognosis and failure to respond to treatment. Whether these associations between versican expression and tumour immunity are the result of a direct role in the pathogenesis of tumours is not clear. In this review, we have focused on the role of versican in the immune response as it relates to tumour progression, with the aim of determining whether our current understanding of the immunobiology of versican warrants further study as a cancer immunotherapy target.
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