Polypyrimidine-tract binding protein 1 (PTBP1) is an important cellular regulator of messenger RNAs influencing the alternative splicing profile of a cell as well as its mRNA stability, location and translation. In addition, it is diverted by some viruses to facilitate their replication. Here, we used a novel PTBP1 knockout mouse to analyse the tissue expression pattern of PTBP1 as well as the effect of its complete removal during development. We found evidence of strong PTBP1 expression in embryonic stem cells and throughout embryonic development, especially in the developing brain and spinal cord, the olfactory and auditory systems, the heart, the liver, the kidney, the brown fat and cartilage primordia. This widespread distribution points towards a role of PTBP1 during embryonic development. Homozygous offspring, identified by PCR and immunofluorescence, were able to implant but were arrested or retarded in growth. At day 7.5 of embryonic development (E7.5) the null mutants were about 5x smaller than the control littermates and the gap in body size widened with time. At mid-gestation, all homozygous embryos were resorbed/degraded. No homozygous mice were genotyped at E12 and the age of weaning. Embryos lacking PTBP1 did not display differentiation into the 3 germ layers and cavitation of the epiblast, which are hallmarks of gastrulation. In addition, homozygous mutants displayed malformed ectoplacental cones and yolk sacs, both early supportive structure of the embryo proper. We conclude that PTBP1 is not required for the earliest isovolumetric divisions and differentiation steps of the zygote up to the formation of the blastocyst. However, further post-implantation development requires PTBP1 and stalls in homozygous null animals with a phenotype of dramatically reduced size and aberration in embryonic and extra-embryonic structures.

In mammals, myocardial cell death due to infarction results in scar formation and little regenerative response. In contrast, zebrafish have a high capacity to regenerate the heart after surgical resection of myocardial tissue. However, whether zebrafish can also regenerate lesions caused by cell death has not been tested. Here, we present a simple method for induction of necrotic lesions in the adult zebrafish heart based on cryoinjury. Despite widespread tissue death and loss of cardiomyocytes caused by these lesions, zebrafish display a robust regenerative response, which results in substantial clearing of the necrotic tissue and little scar formation. The cellular mechanisms underlying regeneration appear to be similar to those activated in response to ventricular resection. In particular, the epicardium activates a developmental gene program, proliferates and covers the lesion. Concomitantly, mature uninjured cardiomyocytes become proliferative and invade the lesion. Our injury model will be a useful tool to study the molecular mechanisms of natural heart regeneration in response to necrotic cell death.

In multitasking, the execution of a prioritized task is in danger of crosstalk by the secondary task. Task shielding allows minimizing this crosstalk. However, the locus and temporal dynamics of crosstalk effects and further sources of influence on the execution of the prioritized task are to-date only vaguely understood. Here we combined a dual-task paradigm with an action dynamics approach and studied how and according to which temporal characteristics crosstalk, previously experienced interference and previously executed responses influenced participants' mouse movements in the prioritized task's execution. Investigating continuous mouse movements of the prioritized task, our results indicate a continuous crosstalk from secondary task processing until the endpoint of the movement was reached, although the secondary task could only be executed after finishing execution of the prioritized task. The motor movement in the prioritized task was further modulated by previously experienced interference between the prioritized and the secondary task. Furthermore, response biases from previous responses of the prioritized and the secondary task in movements indicate different sources of such biases. The bias by previous responses to the prioritized task follows a sustained temporal pattern typical for a contextual reactivation, while the bias by previous responses to the secondary task follows a decaying temporal pattern indicating residual activation of previously activated spatial codes.

Land use transition in dryland ecosystems is one of the major driving forces to landscape change that directly impacts the welfare of humans. In this study, the support vector machine (SVM) classification algorithm and cross tabulation matrix analysis are used to identify systematic and random processes of change. The magnitude and prevailing signals of land use transitions are assessed taking into account net change and swap change. Moreover, spatiotemporal patterns and the relationship of precipitation and the Normalized Difference Vegetation Index (NDVI) are explored to evaluate landscape degradation. The assessment showed that 44% of net change and about 54% of total change occurred during the study period, with the latter being due to swap change. The conversion of over 39% of woodland to cropland accounts for the existence of the highest loss of valuable ecosystem of the region. The spatial relationship of NDVI and precipitation also showed R2 of below 0.5 over 55% of the landscape with no significant changes in the precipitation trend, thus representing an indicative symptom of land degradation. This in-depth analysis of random and systematic landscape change is crucial for designing policy intervention to halt woodland degradation in this fragile environment.

Julie/Julia stands out in several ways. What had begun, in 2002/2003, as a highly popular blog, in which New Yorker Julie Powell tracks her experience of cooking all the recipes in Julia Child’s classic cookbook Mastering the Art of French Cookery, became one of the first notable, commercially successful "blooks"—a neologism that denotes blogs adapted into books. As a visible sign of this achievement, The Ju-lie/Julia Project was awarded with the inaugural “Blooker Prize” in 2006. A few years later, Julie/Julia again pioneered in being the first blog (or blook, for that matter) to be adapted into a Hollywood movie, Nora Ephron’s Julie & Julia. In the following, I want to discuss Julie/Julia, and its adaptations from blog to book to film, as an instructive case study of life writing in the digital age.

The vocal tract shape is crucial to voice production. Its lower part seems particularly relevant for voice timbre. This study analyzes the detailed morphology of parts of the epilaryngeal tube and the hypopharynx for the sustained German vowels /a/, /e/, /i/, /o/, and /u/ by thirteen male singer subjects who were at the beginning of their academic singing studies. Analysis was based on two different phonatory conditions: a natural, speech-like phonation and a singing phonation, like in classical singing. 3D models of the vocal tract were derived from magnetic resonance imaging and compared with long-term average spectrum analysis of audio recordings from the same subjects. Comparison of singing to the speech-like phonation, which served as reference, showed significant adjustments of the lower vocal tract: an average lowering of the larynx by 8 mm and an increase of the hypopharyngeal cross-sectional area (+ 21.9%) and volume (+ 16.8%). Changes in the analyzed epilaryngeal portion of the vocal tract were not significant. Consequently, lower larynx-to-hypopharynx area and volume ratios were found in singing compared to the speech-like phonation. All evaluated measures of the lower vocal tract varied significantly with vowel quality. Acoustically, an increase of high frequency energy in singing correlated with a wider hypopharyngeal area. The findings offer an explanation how classical male singers might succeed in producing a voice timbre with increased high frequency energy, creating a singer‘s formant cluster.

Plastid genomes of photosynthetic flowering plants are usually highly conserved in both structure and gene content. However, the plastomes of parasitic and mycoheterotrophic plants may be released from selective constraint due to the reduction or loss of photosynthetic ability. Here we present the greatly reduced and highly divergent, yet functional, plastome of the nonphotosynthetic holoparasite Hydnora visseri (Hydnoraceae, Piperales). The plastome is 27 kb in length, with 24 genes encoding ribosomal proteins, ribosomal RNAs, tRNAs and a few non-bioenergetic genes, but no genes related to photosynthesis. The inverted repeat and the small single copy region are only ~1.5 kb, and intergenic regions have been drastically reduced. Despite extreme reduction, gene order and orientation are highly similar to the plastome of Piper cenocladum, a related photosynthetic plant in Piperales. Gene sequences in Hydnora are highly divergent and several complementary approaches using the highest possible sensitivity were required for identification and annotation of this plastome. Active transcription is detected for all of the protein coding genes in the plastid genome, and one of two introns is appropriately spliced out of rps12 transcripts. The whole genome shotgun read depth is 1,400X coverage for the plastome, while the mitochondrial genome is covered at 40X and the nuclear genome at 2X. Despite the extreme reduction of the genome and high sequence divergence, the presence of syntenic, long transcriptionally-active open reading frames with distant similarity to other plastid genomes and a high plastome stoichiometry relative to the mitochondrial and nuclear genomes suggests that the plastome remains functional in Hydnora visseri. A four stage model of gene reduction, including the potential for complete plastome loss, is proposed to account for the range of plastid genomes in nonphotosynthetic plants.

A major argument for incorporating deciduous tree species in coniferous forest stands is their role in the amelioration and stabilisation of biogeochemical cycles. Current forest management strategies in central Europe aim to increase the area of mixed stands. In order to formulate statements about the ecological effects of mixtures, studies at the stand level are necessary. In a mixed stand of Norway spruce (Picea abies (L.) Karst.) and silver birch (Betula pendula Roth) in the Ore Mountains (Saxony, Germany), the effects of these two tree species on chemical and microbial parameters in the topsoil were studied at one site in the form of a case study. Samples were taken from the O layer and A horizon in areas of the stand influenced by either birch, spruce or a mixture of birch and spruce. The microbial biomass, basal respiration, metabolic quotient, pH-value and the C and N contents and stocks were analysed in the horizons Of, Oh and A. Significantly higher contents of microbial N were observed in the Of and Oh horizons in the birch and in the spruce-birch strata than in the stratum containing only spruce. The same was found with respect to pH-values in the Of horizon and basal respiration in the Oh horizon. Compared to the spruce stratum, in the birch and spruce-birch strata, significantly lower values were found for the contents of organic C and total N in the A horizon. The findings of the case study indicated that single birch trees have significant effects on the chemical and microbial topsoil properties in spruce-dominated stands. Therefore, the admixture of birch in spruce stands may distinctly affect nutrient cycling and may also be relevant for soil carbon sequestration. Further studies of these functional aspects are recommended.

Appropriate reactions toward emotional stimuli depend on the distribution of prefrontal attentional resources. In mid-adolescence, prefrontal top-down control systems are less engaged, while subcortical bottom-up emotional systems are more engaged. We used functional magnetic resonance imaging to follow the neural development of attentional distribution, i.e. attending versus ignoring emotional stimuli, in adolescence. 144 healthy adolescents were studied longitudinally at age 14 and 16 while performing a perceptual discrimination task. Participants viewed two pairs of stimuli – one emotional, one abstract – and reported on one pair whether the items were the same or different, while ignoring the other pair. Hence, two experimental conditions were created: "attending emotion/ignoring abstract" and "ignoring emotion/attending abstract". Emotional valence varied between negative, positive, and neutral. Across conditions, reaction times and error rates decreased and activation in the anterior cingulate and inferior frontal gyrus increased from age 14 to 16. In contrast, subcortical regions showed no developmental effect. Activation of the anterior insula increased across ages for attending positive and ignoring negative emotions. Results suggest an ongoing development of prefrontal top-down resources elicited by emotional attention from age 14 to 16 while activity of subcortical regions representing bottom-up processing remains stable.

BACKGROUND: The complexity and scale of the knowledge in the biomedical domain has motivated research work towards mining heterogeneous data from both structured and unstructured knowledge bases. Towards this direction, it is necessary to combine facts in order to formulate hypotheses or draw conclusions about the domain concepts. This work addresses this problem by using indirect knowledge connecting two concepts in a knowledge graph to discover hidden relations between them. The graph represents concepts as vertices and relations as edges, stemming from structured (ontologies) and unstructured (textual) data. In this graph, path patterns, i.e. sequences of relations, are mined using distant supervision that potentially characterize a biomedical relation. RESULTS: It is possible to identify characteristic path patterns of biomedical relations from this representation using machine learning. For experimental evaluation two frequent biomedical relations, namely \"has target\", and \"may treat\", are chosen. Results suggest that relation discovery using indirect knowledge is possible, with an AUC that can reach up to 0.8, a result which is a great improvement compared to the random classification, and which shows that good predictions can be prioritized by following the suggested approach. CONCLUSIONS: Analysis of the results indicates that the models can successfully learn expressive path patterns for the examined relations. Furthermore, this work demonstrates that the constructed graph allows for the easy integration of heterogeneous information and discovery of indirect connections between biomedical concepts.