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Translation of protein from mRNA is a complex multi-step process that occurs at a non-uniform rate. Variability in ribosome speed along an mRNA enables refinement of the proteome and plays a critical role in protein biogenesis. Detailed single protein studies have found both tRNA abundance and mRNA secondary structure as key modulators of translation elongation rate, but recent genome-wide ribosome profiling experiments have not observed significant influence of either on translation efficiency. Here we provide evidence that this results from an inherent trade-off between these factors. We find codons pairing to high-abundance tRNAs are preferentially used in regions of high secondary structure content, while codons read by significantly less abundant tRNAs are located in lowly structured regions. By considering long stretches of high and low mRNA secondary structure in Saccharomyces cerevisiae and Escherichia coli and comparing them to randomized-gene models and experimental expression data, we were able to distinguish clear selective pressures and increased protein expression for specific codon choices. The trade-off between secondary structure and tRNA-concentration based codon choice allows for compensation of their independent effects on translation, helping to smooth overall translational speed and reducing the chance of potentially detrimental points of excessively slow or fast ribosome movement.
Das Streben nach Qualität
(2015)
Qualität ist in den letzten Jahren zu einem intensiv diskutierten Thema im Gesundheitswesen geworden. Nach Hygiene- und Behand lungsskandalen steht vor allem der Krankenhaussektor unter Druck. Und obwohl in den vergangenen 15 Jahren eine ganze Reihe an Mechanismen und Regularien eingeführt wurde, so ist der Bereich nur teilweise erforscht. Dieser Artikel liefert einen Überblick über die Komplexität des Qualitätsbegriffs. Anschließend wird die Landschaft der Instrumente zur Qualitätskontrolle und -sicherung im deutschen Krankenhaussektor vorgestellt. Erkenntnisse aus der internationalen Forschung sollen einen vertieften Einblick in die Wirkungsweise gewähren und weitere Forschungslücken betonen.
The polymorphism of immunogenes of the major histocompatibility complex (MHC) is thought to influence the functional plasticity of immune responses and, consequently, the fitness of populations facing heterogeneous pathogenic pressures. Here, we evaluated MHC variation (allelic richness and divergence) and patterns of selection acting on the two highly polymorphic MHC class II loci (DRB and DQB) in the endangered primate Madame Berthe's mouse lemur (Microcebus berthae). Using 454 pyrosequencing, we examined MHC variation in a total of 100 individuals sampled over 9 years in Kirindy Forest, Western Madagascar, and compared our findings with data obtained previously for its sympatric congener, the grey mouse lemur (Microcebus murinus). These species exhibit a contrasting ecology and demography that were expected to affect MHC variation and molecular signatures of selection. We found a lower allelic richness concordant with its low population density, but a similar level of allelic divergence and signals of historical selection in the rare feeding specialist M. berthae compared to the widespread generalist M. murinus. These findings suggest that demographic factors may exert a stronger influence than pathogen-driven selection on current levels of allelic richness in M. berthae. Despite a high sequence similarity between the two congeners, contrasting selection patterns detected at DQB suggest its potential functional divergence. This study represents a first step toward unravelling factors influencing the adaptive divergence of MHC genes between closely related but ecologically differentiated sympatric lemurs and opens new questions regarding potential functional discrepancy that would explain contrasting selection patterns detected at DQB.
Faunal remains from Palaeolithic sites are important genetic sources to study preglacial and postglacial populations and to investigate the effect of climate change and human impact. Post mortem decay, resulting in fragmented and chemically modified DNA, is a key obstacle in ancient DNA analyses. In the absence of reliable methods to determine the presence of endogenous DNA in sub-fossil samples, temporal and spatial surveys of DNA survival on a regional scale may help to estimate the potential of faunal remains from a given time period and region. We therefore investigated PCR amplification success, PCR performance and post mortem damage in c. 47,000 to c. 12,000-year-old horse remains from 14 Palaeolithic sites along the Swiss Jura Mountains in relation to depositional context, tissue type, storage time and age, potentially influencing DNA preservation. The targeted 75 base pair mitochondrial DNA fragment could be amplified solely from equid remains from caves and not from any of the open dry and (temporary) wetland sites. Whether teeth are better than bones cannot be ultimately decided; however, both storage time after excavation and age significantly affect PCR amplification and performance, albeit not in a linear way. This is best explained by the—inevitable—heterogeneity of the data set. The extent of post mortem damage is not related to any of the potential impact factors. The results encourage comprehensive investigations of Palaeolithic cave sites, even from temperate regions.
The ICDP "PaleoVan" drilling campaign at Lake Van, Turkey, provided a long (> 100 m) record of lacustrine subsurface sedimentary microbial cell abundance. After the ICDP campaign at Potrok Aike, Argentina, this is only the second time deep lacustrine cell counts have been documented. Two sites were cored and revealed a strikingly similar cell distribution despite differences in organic matter content and microbial activity. Although shifted towards higher values, cell counts from Lake Potrok Aike, Argentina, reveal very similar distribution patterns with depth. The lacustrine cell count data are significantly different from published marine records; the most probable cause is differences in sedimentary organic matter composition with marine sediments containing a higher fraction of labile organic matter. Previous studies showed that microbial activity and abundance increase centimetres to metres around geologic interfaces. The finely laminated Lake Van sediment allowed studying this phenomenon on the microscale. We sampled at the scale of individual laminae, and in some depth intervals, we found large differences in microbial abundance between the different laminae. This small-scale heterogeneity is normally overlooked due to much larger sampling intervals that integrate over several centimetres. However, not all laminated intervals exhibit such large differences in microbial abundance, and some non-laminated horizons show large variability on the millimetre scale as well. The reasons for such contrasting observations remain elusive, but indicate that heterogeneity of microbial abundance in subsurface sediments has not been taken into account sufficiently. These findings have implications not just for microbiological studies but for geochemistry as well, as the large differences in microbial abundance clearly show that there are distinct microhabitats that deviate considerably from the surrounding layers.
The microbial community populating the human digestive tract has been linked to the development of obesity, diabetes and liver diseases. Proposed mechanisms on how the gut microbiota could contribute to obesity and metabolic diseases include: (1) improved energy extraction from diet by the conversion of dietary fibre to SCFA; (2) increased intestinal permeability for bacterial lipopolysaccharides (LPS) in response to the consumption of high-fat diets resulting in an elevated systemic LPS level and low-grade inflammation. Animal studies indicate differences in the physiologic effects of fermentable and non-fermentable dietary fibres as well as differences in long-and short-term effects of fermentable dietary fibre. The human intestinal microbiome is enriched in genes involved in the degradation of indigestible polysaccharides. The extent to which dietary fibres are fermented and in which molar ratio SCFA are formed depends on their physicochemical properties and on the individual microbiome. Acetate and propionate play an important role in lipid and glucose metabolism. Acetate serves as a substrate for de novo lipogenesis in liver, whereas propionate can be utilised for gluconeogenesis. The conversion of fermentable dietary fibre to SCFA provides additional energy to the host which could promote obesity. However, epidemiologic studies indicate that diets rich in fibre rather prevent than promote obesity development. This may be due to the fact that SCFA are also ligands of free fatty acid receptors (FFAR). Activation of FFAR leads to an increased expression and secretion of enteroendocrine hormones such as glucagon-like-peptide 1 or peptide YY which cause satiety. In conclusion, the role of SCFA in host energy balance needs to be re-evaluated.
Although morphosyntax has been identified as a major source of difficulty for adult (nonnative) language learners, most previous studies have examined a limited set of largely affix-based phenomena. Little is known about word-based morphosyntax in late bilinguals and of how morphosyntax is represented and processed in a nonnative speaker's lexicon. To address these questions, we report results from two behavioral experiments investigating stem variants of strong verbs in German (which encode features such as tense, person, and number) in groups of advanced adult learners as well as native speakers of German. Although the late bilinguals were highly proficient in German, the results of a lexical priming experiment revealed clear native-nonnative differences. We argue that lexical representation and processing relies less on morphosyntactic information in a nonnative than in a native language.
This article investigates a public debate in Germany that put a special spotlight on the interaction of standard language ideologies with social dichotomies, centering on the question of whether Kiezdeutsch, a new way of speaking in multilingual urban neighbourhoods, is a legitimate German dialect. Based on a corpus of emails and postings to media websites, I analyse central topoi in this debate and an underlying narrative on language and identity. Central elements of this narrative are claims of cultural elevation and cultural unity for an idealised standard language High German', a view of German dialects as part of a national folk culture, and the construction of an exclusive in-group of German' speakers who own this language and its dialects. The narrative provides a potent conceptual frame for the Othering of Kiezdeutsch and its speakers, and for the projection of social and sometimes racist deliminations onto the linguistic plane.
Abstract gringo
(2015)
This paper defines the syntax and semantics of the input language of the ASP grounder gringo. The definition covers several constructs that were not discussed in earlier work on the semantics of that language, including intervals, pools, division of integers, aggregates with non-numeric values, and lparse-style aggregate expressions. The definition is abstract in the sense that it disregards some details related to representing programs by strings of ASCII characters. It serves as a specification for gringo from Version 4.5 on.
The effect of implicitly incentivized faking on explicit and implicit measures of doping attitude
(2015)
The Implicit Association Test (IAT) aims to measure participants' automatic evaluation of an attitude object and is useful especially for the measurement of attitudes related to socially sensitive subjects, e.g. doping in sports. Several studies indicate that IAT scores can be faked on instruction. But fully or semi-instructed research scenarios might not properly reflect what happens in more realistic situations, when participants secretly decide to try faking the test. The present study is the first to investigate IAT faking when there is only an implicit incentive to do so. Sixty-five athletes (22.83 years +/- 2.45; 25 women) were randomly assigned to an incentive-to-fake condition or a control condition. Participants in the incentive-to-fake condition were manipulated to believe that athletes with lenient doping attitudes would be referred to a tedious 45-minute anti-doping program. Attitudes were measured with the pictorial doping brief IAT (BIAT) and with the Performance Enhancement Attitude Scale (PEAS). A one-way MANOVA revealed significant differences between conditions after the manipulation in PEAS scores, but not in the doping BIAT. In the light of our hypothesis this suggests that participants successfully faked an exceedingly negative attitude to doping when completing the PEAS, but were unsuccessful in doing so on the reaction time-based test. This study assessed BIAT faking in a setting that aimed to resemble a situation in which participants want to hide their attempts to cheat. The two measures of attitude were differentially affected by the implicit incentive. Our findings provide evidence that the pictorial doping BIAT is relatively robust against spontaneous and naive faking attempts. (B) IATs might be less prone to faking than implied by previous studies.
Based on niche theory, closely related and morphologically similar species are not predicted to coexist due to overlap in resource and habitat use. Local assemblages of bats often contain cryptic taxa, which co-occur despite notable similarities in morphology and ecology. We measured in two different habitat types on Madagascar levels of stable carbon and nitrogen isotopes in hair (n = 103) and faeces (n = 57) of cryptic Vespertilionidae taxa to indirectly examine whether fine-grained trophic niche differentiation explains their coexistence. In the dry deciduous forest (Kirindy), six sympatric species ranged over 6.0% in delta N-15, i.e. two trophic levels, and 4.2% in delta C-13 with a community mean of 11.3% in delta N-15 and - 21.0% in delta C-13. In the mesic forest (Antsahabe), three sympatric species ranged over one trophic level (delta N-15: 2.4%, delta C-13: 1.0%) with a community mean of 8.0% delta N-15 and - 21.7% in delta C-13. Multivariate analyses and residual permutation of Euclidian distances in delta C-13- delta N-15 bi-plots revealed in both communities distinct stable isotope signatures and species separation for the hair samples among coexisting Vespertilionidae. Intraspecific variation in faecal and hair stable isotopes did not indicate that seasonal migration might relax competition and thereby facilitate the local co-occurrence of sympatric taxa.
aspeed
(2015)
Although Boolean Constraint Technology has made tremendous progress over the last decade, the efficacy of state-of-the-art solvers is known to vary considerably across different types of problem instances, and is known to depend strongly on algorithm parameters. This problem was addressed by means of a simple, yet effective approach using handmade, uniform, and unordered schedules of multiple solvers in ppfolio, which showed very impressive performance in the 2011 Satisfiability Testing (SAT) Competition. Inspired by this, we take advantage of the modeling and solving capacities of Answer Set Programming (ASP) to automatically determine more refined, that is, nonuniform and ordered solver schedules from the existing benchmarking data. We begin by formulating the determination of such schedules as multi-criteria optimization problems and provide corresponding ASP encodings. The resulting encodings are easily customizable for different settings, and the computation of optimum schedules can mostly be done in the blink of an eye, even when dealing with large runtime data sets stemming from many solvers on hundreds to thousands of instances. Also, the fact that our approach can be customized easily enabled us to swiftly adapt it to generate parallel schedules for multi-processor machines.
Background: Continuous treatment is an important indicator of medication adherence in dementia. However, long-term studies in larger clinical settings are lacking, and little is known about moderating effects of patient and service characteristics.
Methods: Data from 12,910 outpatients with dementia (mean age 79.2 years; SD = 7.6 years) treated between January 2003 and December 2013 in Germany were included. Continuous treatment was analysed using Kaplan-Meier curves and log-rank tests. In addition, multivariate Cox regression models were fitted with continuous treatment as dependent variable and the predictors antidementia agent, age, gender, medical comorbidities, physician specialty, and health insurance status.
Results: After one year of follow-up, nearly 60% of patients continued drug treatment. Donezepil (HR: 0.88; 95% CI: 0.82-0.95) and memantine (HR: 0.85; 0.79-0.91) patients were less likely to be discontinued treatment as compared to rivastigmine users. Patients were less likely to be discontinued if they were treated by specialist physicians as compared to general practitioners (HR: 0.44; 0.41-0.48). Younger male patients and patients who had private health insurance had a lower discontinuation risk. Regarding comorbidity, patients were more likely to be continuously treated with the index substance if a diagnosis of heart failure or hypertension had been diagnosed at baseline.
Conclusions: Our results imply that besides type of antidementia agent, involvement of a specialist in the complex process of prescribing antidementia drugs can provide meaningful benefits to patients, in terms of more disease-specific and continuous treatment.
The recently proposed global monsoon hypothesis interprets monsoon systems as part of one global-scale atmospheric overturning circulation, implying a connection between the regional monsoon systems and an in-phase behaviour of all northern hemispheric monsoons on annual timescales (Trenberth et al., 2000). Whether this concept can be applied to past climates and variability on longer timescales is still under debate, because the monsoon systems exhibit different regional characteristics such as different seasonality (i. e. onset, peak and withdrawal). To investigate the interconnection of different monsoon systems during the pre-industrial Holocene, five transient global climate model simulations have been analysed with respect to the rainfall trend and variability in different sub-domains of the Afro-Asian monsoon region. Our analysis suggests that on millennial timescales with varying orbital forcing, the monsoons do not behave as a tightly connected global system. According to the models, the Indian and North African monsoons are coupled, showing similar rainfall trend and moderate correlation in centennial rainfall variability in all models. The East Asian monsoon changes independently during the Holocene. The dissimilarities in the seasonality of the monsoon sub-systems lead to a stronger response of the North African and Indian monsoon systems to the Holocene insolation forcing than of the East Asian monsoon and affect the seasonal distribution of Holocene rainfall variations. Within the Indian and North African monsoon domain, precipitation solely changes during the summer months, showing a decreasing Holocene precipitation trend. In the East Asian monsoon region, the precipitation signal is determined by an increasing precipitation trend during spring and a decreasing precipitation change during summer, partly balancing each other. A synthesis of reconstructions and the model results do not reveal an impact of the different seasonality on the timing of the Holocene rainfall optimum in the different sub-monsoon systems. Rather they indicate locally inhomogeneous rainfall changes and show that single palaeo-records should not be used to characterise the rainfall change and monsoon evolution for entire monsoon sub-systems.
Dual-normal logic programs
(2015)
Disjunctive Answer Set Programming is a powerful declarative programming paradigm with complexity beyond NP. Identifying classes of programs for which the consistency problem is in NP is of interest from the theoretical standpoint and can potentially lead to improvements in the design of answer set programming solvers. One of such classes consists of dual-normal programs, where the number of positive body atoms in proper rules is at most one. Unlike other classes of programs, dual-normal programs have received little attention so far. In this paper we study this class. We relate dual-normal programs to propositional theories and to normal programs by presenting several inter-translations. With the translation from dual-normal to normal programs at hand, we introduce the novel class of body-cycle free programs, which are in many respects dual to head-cycle free programs. We establish the expressive power of dual-normal programs in terms of SE- and UE-models, and compare them to normal programs. We also discuss the complexity of deciding whether dual-normal programs are strongly and uniformly equivalent.
40Ar/39Ar in situ UV laser ablation of white mica, Rb–Sr mineral isochrons and zircon fission track dating were applied to determine ages of very low- to low-grade metamorphic processes at 3.5±0.4 kbar, 280±30°C in the Avalonian Mira terrane of SE Cape Breton Island (Nova Scotia). The Mira terrane comprises Neoproterozoic volcanic-arc rocks overlain by Cambrian sedimentary rocks. Crystallization of metamorphic white mica was dated in six metavolcanic samples by 40Ar/39Ar spot age peaks between 396±3 and 363±14 Ma. Rb–Sr systematics of minerals and mineral aggregates yielded two isochrons at 389±7 Ma and 365±8 Ma, corroborating equilibrium conditions during very low- to low-grade metamorphism. The dated white mica is oriented parallel to foliations produced by sinistral strike-slip faulting and/or folding related to the Middle–Late Devonian transpressive assembly of Avalonian terranes during convergence and emplacement of the neighbouring Meguma terrane. Exhumation occurred earlier in the NW Mira terrane than in the SE. Transpression was related to the closure of the Rheic Ocean between Gondwana and Laurussia by NW-directed convergence. The 40Ar/39Ar spot age spectra also display relict age peaks at 477–465 Ma, 439 Ma and 420–428 Ma attributed to deformation and fluid access, possibly related to the collision of Avalonia with composite Laurentia or to earlier Ordovician–Silurian rifting. Fission track ages of zircon from Mira terrane samples range between 242±18 and 225±21 Ma and reflect late Palaeozoic reburial and reheating close to previous peak metamorphic temperatures under fluid-absent conditions during rifting prior to opening of the Central Atlantic Ocean.
The Strange-tailed Tyrant Alectrurus risora (Aves: Tyrannidae) is an endemic species of southern South American grasslands that suffered a 90% reduction of its original distribution due to habitat transformation. This has led the species to be classified as globally Vulnerable. By the beginning of the last century, populations were partially migratory and moved south during the breeding season. Currently, the main breeding population inhabits the Ibera wetlands in the province of Corrientes, north-east Argentina, where it is resident all year round. There are two remaining small populations in the province of Formosa, north-east Argentina, and in southern Paraguay, which are separated from the main population by the Parana-Paraguay River and its continuous riverine forest habitat. The populations of Corrientes and Formosa are separated by 300 km and the grasslands between populations are non-continuous due to habitat transformation. We used mtDNA sequences and eight microsatellite loci to test if there were evidences of genetic isolation between Argentinean populations. We found no evidence of genetic structure between populations (Phi(ST) = 0.004, P = 0.32; Fst = 0.01, P = 0.06), which can be explained by either retained ancestral polymorphism or by dispersal between populations. We found no evidence for a recent demographic bottleneck in nuclear loci. Our results indicate that these populations could be managed as a single conservation unit on a regional scale. Conservation actions should be focused on preserving the remaining network of areas with natural grasslands to guarantee reproduction, dispersal and prevent further decline of populations.
Although morphosyntax has been identified as a major source of difficulty for adult (nonnative) language learners, most previous studies have examined a limited set of largely affix-based phenomena. Little is known about word-based morphosyntax in late bilinguals and of how morphosyntax is represented and processed in a nonnative speaker's lexicon. To address these questions, we report results from two behavioral experiments investigating stem variants of strong verbs in German (which encode features such as tense, person, and number) in groups of advanced adult learners as well as native speakers of German. Although the late bilinguals were highly proficient in German, the results of a lexical priming experiment revealed clear native-nonnative differences. We argue that lexical representation and processing relies less on morphosyntactic information in a nonnative than in a native language.
Drawing on phonology research within the generative linguistics tradition, stochastic methods, and notions from complex systems, we develop a modelling paradigm linking phonological structure, expressed in terms of syllables, to speech movement data acquired with 3D electromagnetic articulography and X-ray microbeam methods. The essential variable in the models is syllable structure. When mapped to discrete coordination topologies, syllabic organization imposes systematic patterns of variability on the temporal dynamics of speech articulation. We simulated these dynamics under different syllabic parses and evaluated simulations against experimental data from Arabic and English, two languages claimed to parse similar strings of segments into different syllabic structures. Model simulations replicated several key experimental results, including the fallibility of past phonetic heuristics for syllable structure, and exposed the range of conditions under which such heuristics remain valid. More importantly, the modelling approach consistently diagnosed syllable structure proving resilient to multiple sources of variability in experimental data including measurement variability, speaker variability, and contextual variability. Prospects for extensions of our modelling paradigm to acoustic data are also discussed.
There is growing recognition of strong periglacial control on bedrock erosion in mountain landscapes, including the shaping of low-relief surfaces at high elevations (summit flats). But, as yet, the hypothesis that frost action was crucial to the assumed Late Cenozoic rise in erosion rates remains compelling and untested. Here we present a landscape evolution model incorporating two key periglacial processes - regolith production via frost cracking and sediment transport via frost creep - which together are harnessed to variations in temperature and the evolving thickness of sediment cover. Our computational experiments time-integrate the contribution of frost action to shaping mountain topography over million-year timescales, with the primary and highly reproducible outcome being the development of flattish or gently convex summit flats. A simple scaling of temperature to marine delta O-18 records spanning the past 14 Myr indicates that the highest summit flats in mid-to high-latitude mountains may have formed via frost action prior to the Quaternary. We suggest that deep cooling in the Quaternary accelerated mechanical weathering globally by significantly expanding the area subject to frost. Further, the inclusion of subglacial erosion alongside periglacial processes in our computational experiments points to alpine glaciers increasing the long-term efficiency of frost-driven erosion by steepening hillslopes.