A unified mechanism for intron and exon definition and back-splicing.

The molecular mechanisms of exon definition and back-splicing are fundamental unanswered questions in pre-mRNA splicing. Here we report cryo-electron microscopy structures of the yeast spliceosomal E complex assembled on introns, providing a view of the earliest event in the splicing cycle that commits pre-mRNAs to splicing. The E complex architecture suggests that the same spliceosome can assemble across an exon, and that it either remodels to span an intron for canonical linear splicing (typically on short exons) or catalyses back-splicing to generate circular RNA (on long exons). The model is supported by our experiments, which show that an E complex assembled on the middle exon of yeast EFM5 or HMRA1 can be chased into circular RNA when the exon is sufficiently long. This simple model unifies intron definition, exon definition, and back-splicing through the same spliceosome in all eukaryotes and should inspire experiments in many other systems to understand the mechanism and regulation of these processes

Target specificity among canonical nuclear poly(A) polymerases in plants modulates organ growth and pathogen response

Polyadenylation of pre-mRNAs is critical for efficient nuclear export, stability, and translation of the mature mRNAs, and thus for gene expression. The bulk of pre-mRNAs are processed by canonical nuclear poly(A) polymerase (PAPS). Both vertebrate and higher-plant genomes encode more than one isoform of this enzyme, and these are coexpressed in different tissues. However, in neither case is it known whether the isoforms fulfill different functions or polyadenylate distinct subsets of pre-mRNAs. Here we show that the three canonical nuclear PAPS isoforms in Arabidopsis are functionally specialized owing to their evolutionarily divergent C-terminal domains. A strong loss-of-function mutation in PAPS1 causes a male gametophytic defect, whereas a weak allele leads to reduced leaf growth that results in part from a constitutive pathogen response. By contrast, plants lacking both PAPS2 and PAPS4 function are viable with wild-type leaf growth. Polyadenylation of SMALL AUXIN UP RNA (SAUR) mRNAs depends specifically on PAPS1 function. The resulting reduction in SAUR activity in paps1 mutants contributes to their reduced leaf growth, providing a causal link between polyadenylation of specific pre-mRNAs by a particular PAPS isoform and plant growth. This suggests the existence of an additional layer of regulation in plant and possibly vertebrate gene expression, whereby the relative activities of canonical nuclear PAPS isoforms control de novo synthesized poly(A) tail length and hence expression of specific subsets of mRNAs

An fMRI study

Background Maternal sensitive behavior depends on recognizing one’s own child’s affective states. The present study investigated distinct and overlapping neural responses of mothers to sad and happy facial expressions of their own child (in comparison to facial expressions of an unfamiliar child). Methods We used functional MRI to measure dissociable and overlapping activation patterns in 27 healthy mothers in response to happy, neutral and sad facial expressions of their own school-aged child and a gender- and age- matched unfamiliar child. To investigate differential activation to sad compared to happy faces of one’s own child, we used interaction contrasts. During the scan, mothers had to indicate the affect of the presented face. After scanning, they were asked to rate the perceived emotional arousal and valence levels for each face using a 7-point Likert-scale (adapted SAM version). Results While viewing their own child’s sad faces, mothers showed activation in the amygdala and anterior cingulate cortex whereas happy facial expressions of the own child elicited activation in the hippocampus. Conjoint activation in response to one’s own child happy and sad expressions was found in the insula and the superior temporal gyrus. Conclusions Maternal brain activations differed depending on the child’s affective state. Sad faces of the own child activated areas commonly associated with a threat detection network, whereas happy faces activated reward related brain areas. Overlapping activation was found in empathy related networks. These distinct neural activation patterns might facilitate sensitive maternal behavior

Hydrothermal circulation at the Cleft-Vance overlapping spreading center : results of a magnetometric resistivity survey

We report on a magnetometric resistivity sounding carried out in the overlapping spreading center between the Cleft and Vance segments of the Juan de Fuca Ridge. The data collected reveal a strong three dimensionality in the crustal electrical resistivity structure on wavelengths of a few kilometers. Areas of reduced crustal electrical resistivities, with values approaching that of seawater, are seen beneath the neovolcanic zones of both active spreading centers. We interpret these reduced resistivities as evidence of active hydrothermal circulation within the uppermost 1 km of hot, young oceanic crust

Tropical coastal habitats as surrogates of fish community structure, grazing, and fisheries value

Habitat maps are frequently invoked as surrogates of biodiversity to aid the design of networks of marine reserves. Maps are used to maximize habitat heterogeneity in reserves because this is likely to maximize the number of species protected. However, the technique's efficacy is limited by intra-habitat variability in the species present and their abundances. Although communities are expected to vary among patches of the same habitat, this variability is poorly documented and rarely incorporated into reserve planning. To examine intra-habitat variability in coral-reef fishes, we generated a data set from eight tropical coastal habitats and six islands in the Bahamian archipelago using underwater visual censuses. Firstly, we provide further support for habitat heterogeneity as a surrogate of biodiversity as each predefined habitat type supported a distinct assemblage of fishes. Intrahabitat variability in fish community structure at scales of hundreds of kilometers (among islands) was significant in at least 75% of the habitats studied, depending on whether presence/absence, density, or biomass data were used. Intra-habitat variability was positively correlated with the mean number of species in that habitat when density and biomass data were used. Such relationships provide a proxy for the assessment of intra-habitat variability when detailed quantitative data are scarce. Intra-habitat variability was examined in more detail for one habitat (forereefs visually dominated by Montastraea corals). Variability in community structure among islands was driven by small, demersal families (e. g., territorial pomacentrid and labrid fishes). Finally, we examined the ecological and economic significance of intra-habitat variability in fish assemblages on Montastraea reefs by identifying how this variability affects the composition and abundances of fishes in different functional groups, the key ecosystem process of parrotfish grazing, and the ecosystem service of value of commercially important finfish. There were significant differences in a range of functional groups and grazing, but not fisheries value. Variability at the scale of tens of kilometers (among reefs around an island) was less than that among islands. Caribbean marine reserves should be replicated at scales of hundreds of kilometers, particularly for species-rich habitats, to capture important intra-habitat variability in community structure, function, and an ecosystem process

Strengthening confidence in climate change impact science

Aim: To assess confidence in conclusions about climate-driven biological change through time, and identify approaches for strengthening confidence scientific conclusions about ecological impacts of climate change. Location: Global. Methods: We outlined a framework for strengthening confidence in inferences drawn from biological climate impact studies through the systematic integration of prior expectations, long-term data and quantitative statistical procedures. We then developed a numerical confidence index (Cindex) and used it to evaluate current practices in 208 studies of marine climate impacts comprising 1735 biological time series. Results: Confidence scores for inferred climate impacts varied widely from 1 to 16 (very low to high confidence). Approximately 35% of analyses were not associated with clearly stated prior expectations and 65% of analyses did not test putative non-climate drivers of biological change. Among the highest-scoring studies, 91% tested prior expectations, 86% formulated expectations for alternative drivers but only 63% statistically tested them. Higher confidence scores observed in studies that did not detect a change or tracked multiple species suggest publication bias favouring impact studies that are consistent with climate change. The number of time series showing climate impacts was a poor predictor of average confidence scores for a given group, reinforcing that vote-counting methodology is not appropriate for determining overall confidence in inferences. Main conclusions: Climate impacts research is expected to attribute biological change to climate change with measurable confidence. Studies with long-term, high-resolution data, appropriate statistics and tests of alternative drivers earn higher Cindex scores, suggesting these should be given greater weight in impact assessments. Together with our proposed framework, the results of our Cindex analysis indicate how the science of detecting and attributing biological impacts to climate change can be strengthened through the use of evidence-based prior expectations and thorough statistical analyses, even when data are limited, maximizing the impact of the diverse and growing climate change ecology literature

Mudanças nos compostos bioativos e atividade antioxidante de pimentas da região amazônica.

A Embrapa Amazônia Oriental possui um Banco Ativo de Pimenteira com diferentes genótipos do gênero Capsicum, os quais ainda não foram analisados, quanto às suas características funcionais e capacidade antioxidante. Este estudo objetivou determinar os teores de ácido ascórbico, compostos fenólicos, carotenoides totais e a atividade antioxidante total, em frutos imaturos e maduros de genótipos de pimentas Capsicum spp. As concentrações de vitamina C (100,76-361,65 mg 100 g-1 nos frutos imaturos e 36,70-157,76 mg 100 g-1 nos maduros) decresceram com a maturação dos frutos. Carotenoides totais não foram detectados nos frutos imaturos, porém, nos frutos maduros, observaram-se valores de 73,80-1349,97 mg g-1, em função do genótipo. Os teores de compostos fenólicos aumentaram nos frutos maduros (147,40-718,64 mg GAE 100 g-1), para oito dos nove genótipos avaliados. Os frutos de pimenteira apresentaram significativa atividade antioxidante (55,02-92,03 mM trolox g-1 nos frutos imaturos e 39,60-113,08 mM trolox g- 1 nos maduros). Concluiu-se que o grau de maturação dos frutos influenciou nos teores de compostos bioativos dos genótipos estudados. Destacaram-se, como genótipos promissores com potencial para serem utilizados em programas de melhoramento genético, IAN-186301 e IAN-186324, pelos altos teores de carotenoides totais; IAN-186301, IAN-186311, IAN-186312 e IAN-186313, com relação às altas concentrações de ácido ascórbico; IAN-186304 e IAN-186311, pelos altos teores de compostos fenólicos; e IAN-186311, para atividade antioxidante

Implicit trust in clinical decision-making by multidisciplinary teams

In clinical practice, decision-making is not performed by individual knowers but by an assemblage of people and instruments in which no one member has full access to every piece of evidence. This is due to decision making teams consisting of members with different kinds of expertise, as well as to organisational and time constraints. This raises important questions for the epistemology of medicine, which is inherently social in this kind of setting, and implies epistemic dependence on others. Trust in these contexts is a highly complex social practice, involving different forms of relationships between trust and reasons for trust: based on reasons, and not based on reasons; based on reasons that are easily accessible to reflection and others that are not. In this paper, we focus on what it means to have reasons to trust colleagues in an established clinical team, collectively supporting or carrying out every day clinical decision-making. We show two important points about these reasons, firstly, they are not sought or given in advance of a situation of epistemic dependence, but are established within these situations; secondly they are implicit in the sense of being contained or nested within other actions that are not directly about trusting another person. The processes of establishing these reasons are directly about accomplishing a task, and indirectly about trusting someone else’s expertise or competence. These processes establish a space of reasons within which what it means to have reasons for trust, or not, gains a meaning and traction in these team-work settings. Based on a qualitative study of decision-making in image assisted diagnosis and treatment of a complex disease called pulmonary hypertension (PH), we show how an intersubjective framework, or ‘space of reasons’ is established through team members forging together a common way of identifying and dealing with evidence. In dealing with images as a central diagnostic tool, this also involves a common way of looking at the images, a common mode or style of perception. These frameworks are developed through many iterations of adjusting and calibrating interpretations in relation to those of others, establishing what counts as evidence, and ranking different kinds of evidence. Implicit trust is at work throughout this process. Trusting the expertise of others in clinical decision-making teams occurs while the members of the team are busy on other tasks, most importantly, building up a framework of common modes of seeing, and common ways of identifying and assessing evidence emerge. It is only in this way that trusting or mistrusting becomes meaningful in these contexts, and that a framework for epistemic dependence is established

An Environmental and Behavioural Analysis of Arson in a Danish Sample

Abstract Background: Despite its significance as a costly and destructive criminal behaviour, there appears to be some consensus that we know relatively little about arson compared to many other areas of criminal behaviour. Moreover, most existing theory and research into arson has come from the USA, and has tended to concentrate on profiling the characteristics of offenders, rather than investigating, at least in any detail, features of the environment that may influence their behaviour. Aim: The main aim and overarching theme of the current thesis was, therefore, to describe and evaluate some of the main demographic and biographical characteristics, offence related behaviours, and environmental factors associated with arson, in a sample of arson offenders from a European country. Methods: Six empirical studies were conducted, each based on cases drawn from a sample of 746 cases committed by 540 offenders from Denmark between 2002 and 2010 in two police districts, one rural and one urban. Studies 1 and 2 examined a range of demographic and biographical characteristics of arson offenders (such as, gender and age); Studies 3 and 4 covered offence related behaviours (such as selection of targets, and travel distances), and employed regression analyses to look specifically at how these were predicted by other offence related and demographic and biographical variables. Study 5 then investigated the prediction of serial offending as an indicator of arson recidivism using the above demographic and biographical variables and offence related variables. Finally, Study 6 attempted to employ a new approach, via Google Earth, to examine the influence of a range of architectural and structural features of the environment on arson offending; these included 2 targets, presence of high rise buildings, territorial markers, population density and maintenance. Results and Discussion: Findings supported previous literature in identifying the typical arsonist as a young male offender; however, the results further suggested three possible divergent trends in the data corresponding to different categories of arson offender: 1) a more frequent opportunistic arsonist; 2) a less frequent, but more serious, often more persistent serial offender, and 3) a category of mainly female offenders who are less likely to be serial offenders but who may be reacting to dysfunctional home environments. Importantly, in relation to the latter finding, a bimodal peak in age emerged in the subgroup of female offenders, identifying a younger group of female offenders in their mid and late teen years and an older subgroup of female offenders in their late thirties and early forties. Another notable finding was that young male offenders who were not at school were particularly at risk for becoming serial offenders, suggesting that young males not attending school could be targeted in terms of prevention of persistent arson. Also, as predictors of arson, a number of environmental variables were significant and in line with predictions (for example, arson was more prevalant where there were vacant buildings, and very significantly, where the nearest police station was farthest away), but others were significant in a direction opposite to predictions (high building density was associated with lower rates of arson), and some potentially important predicted relationships failed to emerge as significant predictors (such as territorial markers). In addition to the above, two other major findings emerged. First, whilst it was possible be to predict crime scene behaviours from other crime scene behaviours with some degree of accuracy, and, similarly, demographic behaviours (like previous arson) from other demographic factors, predicting crime scene behaviours from demographic factors and vice versa proved to be considerably more difficult. In contrast, in terms of having 3 maximum impact on arson rates the environmental variables considered here did a relatively good job of predicting the presence of arson. A number of limitations and implications are also discussed. Conclusion Considering the results as a whole, notwithstanding some success in predicting arson from demographic and offence related variables, it is concluded that an extension of the kind of environmental approach explored in this thesis could potentially be used for developing environmental schemes for arson prevention that might be considerably easier to apply, and perhaps even more effective in reducing arson, than targeting ‘at risk’ groups of individuals