A directed approach for the identification of transcripts harbouring the spliced leader sequence and the effect of trans-splicing knockdown in Schistosoma mansoni

Schistosomiasis is a major neglected tropical disease caused by trematodes from the genus Schistosoma. Because schistosomes exhibit a complex life cycle and numerous mechanisms for regulating gene expression, it is believed that spliced leader (SL) trans-splicing could play an important role in the biology of these parasites. The purpose of this study was to investigate the function of trans-splicing in Schistosoma mansoni through analysis of genes that may be regulated by this mechanism and via silencing SL-containing transcripts through RNA interference. Here, we report our analysis of SL transcript-enriched cDNA libraries from different S. mansoni life stages. Our results show that the trans-splicing mechanism is apparently not associated with specific genes, subcellular localisations or life stages. In cross-species comparisons, even though the sets of genes that are subject to SL trans-splicing regulation appear to differ between organisms, several commonly shared orthologues were observed. Knockdown of trans-spliced transcripts in sporocysts resulted in a systemic reduction of the expression levels of all tested trans-spliced transcripts; however, the only phenotypic effect observed was diminished larval size. Further studies involving the findings from this work will provide new insights into the role of trans-splicing in the biology of S. mansoni and other organisms. All Expressed Sequence Tags generated in this study were submitted to dbEST as five different libraries. The accessions for each library and for the individual sequences are as follows: (i) adult worms of mixed sexes (LIBEST_027999: JZ139310 - JZ139779), (ii) female adult worms (LIBEST_028000: JZ139780 - JZ140379), (iii) male adult worms (LIBEST_028001: JZ140380 - JZ141002), (iv) eggs (LIBEST_028002: JZ141003 - JZ141497) and (v) schistosomula (LIBEST_028003: JZ141498 - JZ141974).

Hes1 regulates corneal development and the function of corneal epithelial stem/progenitor cells.

Hes1, a major target gene in Notch signaling, regulates the fate and differentiation of various cell types in many developmental systems. To gain a novel insight into the role of Hes1 in corneal tissue, we performed gain-of-function and loss-of-function studies. We show that corneal development was severely disturbed in Hes1-null mice. Hes1-null corneas manifested abnormal junctional specialization, cell differentiation, and less cell proliferation ability. Worthy of note, Hes1 is expressed mainly in the corneal epithelial stem/progenitor cells and is not detected in the differentiated corneal epithelial cells. Expression of Hes1 is closely linked with corneal epithelial stem/progenitor cell proliferation activity in vivo. Moreover, forced Hes1 expression inhibits the differentiation of corneal epithelial stem/progenitor cells and maintains these cells' undifferentiated state. Our data provide the first evidence that Hes1 regulates corneal development and the homeostatic function of corneal epithelial stem/progenitor cells.

Interaction of lipophorin with Rhodnius prolixus oocytes: biochemical properties and the importance of blood feeding

Lipophorin (Lp) is the main haemolymphatic lipoprotein in insects and transports lipids between different organs. In adult females, lipophorin delivers lipids to growing oocytes. In this study, the interaction of this lipoprotein with the ovaries of Rhodnius prolixus was characterised using an oocyte membrane preparation and purified radiolabelled Lp (125I-Lp). Lp-specific binding to the oocyte membrane reached equilibrium after 40-60 min and when 125I-Lp was incubated with increasing amounts of membrane protein, corresponding increases in Lp binding were observed. The specific binding of Lp to the membrane preparation was a saturable process, with a Kdof 7.1 ± 0.9 x 10-8M and a maximal binding capacity of 430 ± 40 ng 125I-Lp/µg of membrane protein. The binding was calcium independent and pH sensitive, reaching its maximum at pH 5.2-5.7. Suramin inhibited the binding interaction between Lp and the oocyte membranes, which was completely abolished at 0.5 mM suramin. The oocyte membrane preparation from R. prolixus also showed binding to Lp from Manduca sexta. When Lp was fluorescently labelled and injected into vitellogenic females, the level of Lp-oocyte binding was much higher in females that were fed whole blood than in those fed blood plasma.

Hierarchic species-area relationships and the management of forest habitat islands in intensive farmland

Habitat loss and fragmentation due to land use changes are major threats to biodiversity in forest ecosystems, and they are expected to have important impacts on many taxa and at various spatial scales. Species richness and area relationships (SARs) have been used to assess species diversity patterns and drivers, and thereby in the establishment of conservation and management strategies. Here we propose a hierarchical approach to achieve deeper insights on SARs in small forest islets in intensive farmland and to address the impacts of decreasing naturalness on such relationships. In the intensive dairy landscapes of Northwest Portugal, where small forest stands (dominated by pines, eucalypts or both) represent semi-natural habitat islands, 50 small forest stands were selected and surveyed for vascular plant diversity. A hierarchical analytical framework was devised to determine species richness and inter- and intra-patch SARs for the whole set of forest patches (general patterns) and for each type of forest (specific patterns). Differences in SARs for distinct groups were also tested by considering subsets of species (native, alien, woody, and herbaceous). Overall, values for species richness were confirmed to be different between forest patches exhibiting different levels of naturalness. Whereas higher values of plant diversity were found in pine stands, higher values for alien species were observed in eucalypt stands. Total area of forest (inter-patch SAR) was found not to have a significant impact on species richness for any of the targeted groups of species. However, significant intra-patch SARs were obtained for all groups of species and forest types. A hierarchical approach was successfully applied to scrutinise SARs along a gradient of forest naturalness in intensively managed landscapes. Dominant canopy tree and management intensity were found to reflect differently on distinct species groups as well as to compensate for increasing stand area, buffering SARs among patches, but not within patches. Thus, the maintenance of small semi-natural patches dominated by pines, under extensive practices of forest management, will promote native plant diversity while at the same time contributing to limit the expansion of problematic alien invasive species.

Suicidal ideation and the risk of suicide in patients with fibromyalgia: a comparison with non-pain controls and patients suffering from low-back pain.

Fibromyalgia is associated with an increased rate of mortality from suicide. In fact, this disease is associated with several characteristics that are linked to an increased risk of suicidal behaviors, such as being female and experiencing chronic pain, psychological distress, and sleep disturbances. However, the literature concerning suicidal behaviors and their risk factors in fibromyalgia is sparse. The objectives of the present study were to evaluate the prevalence of suicidal ideation and the risk of suicide in a sample of patients with fibromyalgia compared with a sample of healthy subjects and a sample of patients with chronic low-back pain. We also aimed to evaluate the relevance of pain intensity, depression, and sleep quality as variables related to suicidal ideation and risks. Logistic regression was applied to estimate the likelihood of suicidal ideation and the risk of suicide adjusted by age and sex. We also used two logistic regression models using age, sex, pain severity score, depression severity, sleep quality, and disease state as independent variables and using the control group as a reference. Forty-four patients with fibromyalgia, 32 patients with low-back pain, and 50 controls were included. Suicidal ideation, measured with item 9 of the Beck Depression Inventory, was almost absent among the controls and was low among patients with low-back pain; however, suicidal ideation was prominent among patients with fibromyalgia (P<0.0001). The risk of suicide, measured with the Plutchik Suicide Risk Scale, was also higher among patients with fibromyalgia than in patients with low-back pain or in controls (P<0.0001). The likelihood for suicidal ideation and the risk of suicide were higher among patients with fibromyalgia (odds ratios of 26.9 and 48.0, respectively) than in patients with low-back pain (odds ratios 4.6 and 4.7, respectively). Depression was the only factor associated with suicidal ideation or the risk of suicide.

Mate choice evolution, dominance effects, and the maintenance of genetic variation.

Female mate choice influences the maintenance of genetic variation by altering the mating success of males with different genotypes. The evolution of preferences themselves, on the other hand, depends on genetic variation present in the population. Few models have tracked this feedback between a choice gene and its effects on genetic variation, in particular when genes that determine offspring viability and attractiveness have dominance effects. Here we build a population genetic model that allows comparing the evolution of various choice rules in a single framework. We first consider preferences for good genes and show that focused preferences for homozygotes evolve more easily than broad preferences, which allow heterozygous males high mating success too. This occurs despite better maintenance of genetic diversity in the latter scenario, and we discuss why empirical findings of superior mating success of heterozygous males consequently do not immediately lead to a better understanding of the lek paradox. Our results thus suggest that the mechanisms that help maintain genetic diversity also have a flipside of making female choice an inaccurate means of producing the desired kind of offspring. We then consider preferences for heterozygosity per se, and show that these evolve only under very special conditions. Choice for compatible genotypes can evolve but its selective advantage diminishes quickly due to frequency-dependent selection. Finally, we show that our model reproduces earlier results on selfing, when the female choice strategy produces assortative mating. Overall, our model indicates that various forms of heterozygote-favouring (or variable) female choice pose a problem for the theory of sexual ornamentation based on indirect benefits, rather than a solution.

Relative clauses in Iraqi Arabic and the status of resumptive pronouns

Not much has been said about the grammar of Iraqi Arabic. This research is an attempt to shed light on the nature of IA relative clauses. The research focuses on the behavior of the resumptive strategy as opposed to the gap strategy. We consider islandhood, Weak and Strong CrossOver, reconstruction and scope binding, in order to further understand the behavior of resumption. The final conclusion reached is that in Iraqi Arabic the resumptive strategy is actually related to the gap strategy in several respects; and in those where it differs we propose that gaps (traces) are replaced by trace+pronoun complex

Insulin and NPY pathways and the control of GnRH function and puberty onset.

Energy balance exerts a critical influence on reproductive function. Leptin and insulin are among the metabolic factors signaling the nutritional status of an individual to the hypothalamus, and their role in the overall modulation of the activity of GnRH neurons is increasingly recognized. As such, they participate to a more generalized phenomenon: the signaling of peripheral metabolic changes to the central nervous system. The physiological importance that the interactions occurring between peripheral metabolic factors and the central nervous system bear for the control of food intake is increasingly recognized. The central mechanisms implicated are the focus of attention of very many research groups worldwide. We review here the experimental data that suggest that similar mechanisms are at play for the metabolic control of the neuroendocrine reproductive function. It is appearing that metabolic signals are integrated at the levels of first-order neurons equipped with the proper receptors, ant that these neurons send their signals towards hypothalamic GnRH neurons which constitute the integrative element of this network.

Weathering and the mobility of phosphorus in the catchments and forefields of the Rhone and Oberaar glaciers, central Switzerland: Implications for the global phosphorus cycle on glacial-interglacial timescales

In this study we evaluate the dynamics of the biophile element phosphorus (P) in the catchment and proglacial areas of the Rhone and Oberaar glaciers (central Switzerland). We analysed erosion and dissolution rates of P-containing minerals in the subglacial environment by sampling water and suspended sediment in glacier outlets during three ablation and two accumulation seasons. We also quantified biogeochemical weathering rates of detrital P in proglacial sedimentary deposits using two chronosequences of samples of fresh, suspended, material obtained from the Oberaar and Rhone water outlets, Little-Ice-Age (LIA) moraines and Younger Dryas (YD) tills in each catchment. Subglacial P weathering is mainly a physical process and detrital P represents more than 99%, of the precipitation-corrected total P denudation flux (234 and 540 kg km(-2) yr(-1) for the Rhone and Oberaar catchments, respectively). The calculated detrital P flux rates are three to almost five times higher than the world average flux. The precipitation-corrected soluble reactive P (SRP) flux corresponds to 1.88-1.99 kg km(-2) yr(-1) (Rhone) and 2.12-2.44 kg km(-2) yr(-1) (Oberaar), respectively. These fluxes are comparable to those of tropical rivers draining transport-limited, tectonically inactive weathering areas. In order to evaluate the efficiency of detrital P weathering in the Rhone and Oberaar proglacial areas, we systematically graded apatite grains extracted from the chronosequence in each catchment relative to weathering-induced changes in their surface morphologies (grades 1-4). Fresh apatite grains are heavily indented and dissolution rounded (grade 1). LIA grains from two 0-10 cm deep moraine samples show extensive dissolution etching, similar to surface grains from the YD profile (mean grades 2.7, 3.5 and 3.5, respectively). In these proglacial deposits, the weathering front deepens progressively as a function of time due to biocorrosion in the evolving acidic pedosphere, with mechanical indentations on grains acting as sites of preferential dissolution. We also measured iron-bound, organic and detrital P concentrations in the chronosequence and show that organic and iron-bound P has almost completely replaced detrital P in the top layers of the YD profiles. Detrital P weathering rates are calculated as 3 10 and 280 kg km(-2) yr(-1) for LIA moraines and 10 kg km(-2) yr(-1) for YD tills. During the first 300 years of glacial sediment exposure P dissolution rates are shown to be approximately 70 times higher than the mean global dissolved P flux from ice-free continents. After 11.6 kyr the flux is 2.5 times the global mean. These data strengthen the argument for substantial changes in the global dissolved P flux on glacial-interglacial timescales. A crude extrapolation from the data described here suggests that the global dissolved P flux may increase by 40-45% during the first few hundred years of a deglaciation phase

Advance directives and the impact of timing. A qualitative study with Swiss general practitioners.

PRINCIPLES: Advance directives are seen as an important tool for documenting the wishes of patients who are no longer competent to make decisions in regards to their medical care. Due to their nature, approaching the subject of advance directives with a patient can be difficult for both the medical care provider and the patient. This paper focuses on general practitioners' perspectives regarding the timing at which this discussion should take place, as well as the advantages and disadvantages of the different moments. METHODS: In 2013, 23 semi-structured face-to-face interviews were performed with Swiss general practitioners. Interviews were analysed using qualitative content analysis. RESULTS: In our sample, 23 general practitioners provided different options that they felt were appropriate moments: either (a) when the patient is still healthy, (b) when illness becomes predominant, or (c) when a patient has been transferred to a long-term care facility. Furthermore, general practitioners reported uncertainty and discomfort regarding initiating the discussion. CONCLUSION: The distinct approaches, perspectives and rationales show that there is no well-defined or "right" moment. However, participants often associated advance directives with death. This link caused discomfort and uncertainty, which led to hesitation and delay on the part of general practitioners. Therefore we recommend further training on how to professionally initiate a conversation about advance directives. Furthermore, based on our results and experience, we recommend an early approach with healthy patients paired with later regular updates as it seems to be the most effective way to inform patients about their end-of-life care options.

Intrusive versus domiciliated triatomines and the challenge of adapting vector control practices against Chagas disease

Chagas disease prevention remains mostly based on triatomine vector control to reduce or eliminate house infestation with these bugs. The level of adaptation of triatomines to human housing is a key part of vector competence and needs to be precisely evaluated to allow for the design of effective vector control strategies. In this review, we examine how the domiciliation/intrusion level of different triatomine species/populations has been defined and measured and discuss how these concepts may be improved for a better understanding of their ecology and evolution, as well as for the design of more effective control strategies against a large variety of triatomine species. We suggest that a major limitation of current criteria for classifying triatomines into sylvatic, intrusive, domiciliary and domestic species is that these are essentially qualitative and do not rely on quantitative variables measuring population sustainability and fitness in their different habitats. However, such assessments may be derived from further analysis and modelling of field data. Such approaches can shed new light on the domiciliation process of triatomines and may represent a key tool for decision-making and the design of vector control interventions.

Suicidal ideation and the risk of suicide in patients with fibromyalgia: a comparison with non-pain controls and patients suffering from low-back pain.

Fibromyalgia is associated with an increased rate of mortality from suicide. In fact, this disease is associated with several characteristics that are linked to an increased risk of suicidal behaviors, such as being female and experiencing chronic pain, psychological distress, and sleep disturbances. However, the literature concerning suicidal behaviors and their risk factors in fibromyalgia is sparse. The objectives of the present study were to evaluate the prevalence of suicidal ideation and the risk of suicide in a sample of patients with fibromyalgia compared with a sample of healthy subjects and a sample of patients with chronic low-back pain. We also aimed to evaluate the relevance of pain intensity, depression, and sleep quality as variables related to suicidal ideation and risks. Logistic regression was applied to estimate the likelihood of suicidal ideation and the risk of suicide adjusted by age and sex. We also used two logistic regression models using age, sex, pain severity score, depression severity, sleep quality, and disease state as independent variables and using the control group as a reference. Forty-four patients with fibromyalgia, 32 patients with low-back pain, and 50 controls were included. Suicidal ideation, measured with item 9 of the Beck Depression Inventory, was almost absent among the controls and was low among patients with low-back pain; however, suicidal ideation was prominent among patients with fibromyalgia (P<0.0001). The risk of suicide, measured with the Plutchik Suicide Risk Scale, was also higher among patients with fibromyalgia than in patients with low-back pain or in controls (P<0.0001). The likelihood for suicidal ideation and the risk of suicide were higher among patients with fibromyalgia (odds ratios of 26.9 and 48.0, respectively) than in patients with low-back pain (odds ratios 4.6 and 4.7, respectively). Depression was the only factor associated with suicidal ideation or the risk of suicide.

State-Society Relationships, Social Trust and the Development of Labour Market Policies in Italy and Sweden

The first decade of the twenty-first century may be remembered for the rebirth of consensus on labour market policy. After three decades of bitter political and ideological controversy between a neo-liberal and a traditional social democratic approach, a new model, often labelled flexicurity, has emerged. This model is promoted by numerous political organisations since it promises to put an end to the old trade-off between equality and efficiency. Several countries are embracing the flexicurity model as a blueprint for labour market reform, but others, mostly belonging to the 'Mediterranean Rim', are clearly lagging behind. Why is it so difficult for these countries to implement the flexicurity model? This paper argues that the application of a flexicurity strategy in these countries is complicated by the lack of social trust between social partners and the state as well as political economy traditions that highlight the role of labour market regulation as a source of social protection.

Calcification des grandes artères et risque de fracture ostéoporotique [Aortic calcification and the risk of osteoporotic fractures].

Osteoporosis and atherosclerosis seem to be epidemiologically correlated. Several medical conditions are risk factors for both osteoporosis and atheromatosis (i.e. age, diabetes, end stage renal disease, sedentarity, smoking), but a common pathogenic link may be present beyond this. The burden of cardiovascular events and of osteoporotic fracture is considerable for the health care system in term of costs and resources. However, both diseases are rarely managed together. This article is a review of the recent studies in this new field.