DAP5 enables main ORF translation on mRNAs with structured and uORF-containing 5' leaders.

Half of mammalian transcripts contain short upstream open reading frames (uORFs) that potentially regulate translation of the downstream coding sequence (CDS). The molecular mechanisms governing these events remain poorly understood. Here, we find that the non-canonical initiation factor Death-associated protein 5 (DAP5 or eIF4G2) is required for translation initiation on select transcripts. Using ribosome profiling and luciferase-based reporters coupled with mutational analysis we show that DAP5-mediated translation occurs on messenger RNAs (mRNAs) with long, structure-prone 5' leader sequences and persistent uORF translation. These mRNAs preferentially code for signalling factors such as kinases and phosphatases. We also report that cap/eIF4F- and eIF4A-dependent recruitment of DAP5 to the mRNA facilitates main CDS, but not uORF, translation suggesting a role for DAP5 in translation re-initiation. Our study reveals important mechanistic insights into how a non-canonical translation initiation factor involved in stem cell fate shapes the synthesis of specific signalling factors

DAP5 enables main ORF translation on mRNAs with structured and uORF-containing 5' leaders

Half of mammalian transcripts contain short upstream open reading frames (uORFs) that potentially regulate translation of the downstream coding sequence (CDS). The molecular mechanisms governing these events remain poorly understood. Here, we find that the non-canonical initiation factor Death-associated protein 5 (DAP5 or eIF4G2) is required for translation initiation on select transcripts. Using ribosome profiling and luciferase-based reporters coupled with mutational analysis we show that DAP5-mediated translation occurs on messenger RNAs (mRNAs) with long, structure-prone 5' leader sequences and persistent uORF translation. These mRNAs preferentially code for signalling factors such as kinases and phosphatases. We also report that cap/eIF4F- and eIF4A-dependent recruitment of DAP5 to the mRNA facilitates main CDS, but not uORF, translation suggesting a role for DAP5 in translation re-initiation. Our study reveals important mechanistic insights into how a non-canonical translation initiation factor involved in stem cell fate shapes the synthesis of specific signalling factors

CD44+ and CD31+ extracellular vesicles (EVs) are significantly reduced in polytraumatized patients with hemorrhagic shock – evaluation of their diagnostic and prognostic potential

BackgroundHemorrhagic shock (HS) is responsible for approximately 2 million deaths per year worldwide and is caused in 80% by polytrauma. These patients need a precise and quick diagnostic, which should be based on a combination of laboratory markers and radiological data. Extracellular vesicles (EVs) were described as potential new markers and mediators in trauma. The aim of the present study was to analyze, whether the surface epitopes of plasma-EVs reflect HS in polytraumatized patients and whether cell-specific EV subpopulations are useful diagnostic tools.Material and methodsPlasma samples from polytraumatized patients (ISS ≥16) with HS (n=10) and without (n=15), were collected at emergency room (ER) and 24h after trauma. Plasma-EVs were isolated via size exclusion chromatography and EV-concentrations were detected by Coomassie Plus (Bradford) Assay. The EVs subpopulations were investigated by a bead-based multiplex flow cytometry measurement of surface epitopes and were compared with healthy controls (n=10). To investigate the diagnostic and prognostic potential of EVs subpopulations, results were correlated with clinical outcome parameters documented in the electronical patients’ record.ResultsWe observed a significant reduction of the total amount of plasma EVs in polytrauma patients with HS, as compared to polytrauma patients without HS and healthy controls. We found significant reduction of CD42a+ and CD41b+ (platelet-derived) EVs in all polytrauma patients, as well as a reduction of CD29+ EVs compared to healthy volunteers (*p<0.05). CD44+ and CD31+ EVs were specifically altered in patients with HS (*p<0.05). Both EV populations showed a moderate correlation (r² = 0.42) with the transfusion of erythrocyte concentrate, were associated with non-survival and the need for catecholamines (*p<0.05).ConclusionOur data reveal that polytrauma patients with a hemorrhagic shock are characterized by a reduction of CD44+ and CD31+ plasma-EVs. Both EV populations showed a moderate correlation with the need of erythrocyte transfusion, were associated with non-survival and the need for catecholamines

Polyphenols-Ensured Accessibility from Food to the Human Metabolism by Chemical and Biotechnological Treatments

Polyphenols are plant-based compounds famous for their positive impact on both human health and the quality of food products. The benefits of polyphenols are related to reducing cardiovascular diseases, cholesterol management, cancers, and neurological disorders in humans and increasing the shelf life, management of oxidation, and anti-microbial activity in food products. The bioavailability and bio-accessibility of polyphenols are of the highest importance to secure their impact on human and food health. This paper summarizes the current state-of-the-art approaches on how polyphenols can be made more accessible in food products to contribute to human health. For example, by using food processing methods including various technologies, such as chemical and biotechnological treatments. Food matrix design and simulation procedures, in combination with encapsulation of fractionated polyphenols utilizing enzymatic and fermentation methodology, may be the future technologies to tailor specific food products with the ability to ensure polyphenol release and availability in the most suitable parts of the human body (bowl, intestine, etc.). The development of such new procedures for utilizing polyphenols, combining novel methodologies with traditional food processing technologies, has the potential to contribute enormous benefits to the food industry and health sector, not only reducing food waste and food-borne illnesses but also to sustain human health

Evaluation of [18F]-FDG-Based Hybrid Imaging Combinations for Assessment of Bone Marrow Involvement in Lymphoma at Initial Staging.

The purpose of our study was to determine the value of different hybrid imaging combinations for the detection of focal and diffuse bone marrow infiltration in lymphoma. Patients with histologically proven lymphoma, who underwent both [18F]-FDG-PET/CT and whole-body MRI (including T1- and diffusion-weighted [DWI] sequences) within seven days, and a subsequent bone marrow biopsy, were retrospectively included. Three hybrid imaging combinations were evaluated: (1) [18F]-FDG-PET/CT; (2) [18F]-FDG-PET/T1; and (3) [18F]-FDG-PET/DWI. The presence of focal or diffuse bone marrow infiltration was assessed by two rater teams. Sensitivity, specificity, and accuracy for the detection of overall, focal, and diffuse bone marrow involvement were compared between the three hybrid imaging combinations. Overall, lymphomatous bone marrow involvement was found in 16/60 patients (focal, 8; diffuse, 8). Overall sensitivity, specificity, and accuracy were 81.3%, 95.5%, and 91.7% for [18F]-FDG-PET/CT; 81.3%, 97.7%, and 93.3% for [18F]-FDG-PET/T1; and 81.3%, 95.5%, and 91.7% for [18F]-FDG-PET/DWI. No statistically significant differences between the three imaging combinations were observed, based on overall bone marrow involvement, focal involvement, or diffuse involvement. The sensitivity of all three imaging combinations for detecting diffuse bone marrow involvement was only moderate (62.5% for all three combinations). Although the combination of [18F]-FDG-PET and T1-weighted MRI generally showed the best diagnostic performance for the detection of bone marrow involvement in lymphoma, it was not significantly superior to the two other hybrid imaging combinations. Since the sensitivity of all imaging combinations for the detection of diffuse bone marrow involvement was only moderate, bone marrow biopsy cannot be replaced by imaging as yet

MR-based morphometry of the posterior fossa in fetuses with neural tube defects of the spine.

OBJECTIVES: In cases of "spina bifida," a detailed prenatal imaging assessment of the exact morphology of neural tube defects (NTD) is often limited. Due to the diverse clinical prognosis and prenatal treatment options, imaging parameters that support the prenatal differentiation between open and closed neural tube defects (ONTDs and CNTDs) are required. This fetal MR study aims to evaluate the clivus-supraocciput angle (CSA) and the maximum transverse diameter of the posterior fossa (TDPF) as morphometric parameters to aid in the reliable diagnosis of either ONTDs or CNTDs. METHODS: The TDPF and the CSA of 238 fetuses (20-37 GW, mean: 28.36 GW) with a normal central nervous system, 44 with ONTDS, and 13 with CNTDs (18-37 GW, mean: 24.3 GW) were retrospectively measured using T2-weighted 1.5 Tesla MR -sequences. RESULTS: Normal fetuses showed a significant increase in the TDPF (r = .956; p<.001) and CSA (r = .714; p<.001) with gestational age. In ONTDs the CSA was significantly smaller (p<.001) than in normal controls and CNTDs, whereas in CNTDs the CSA was not significantly smaller than in controls (p = .160). In both ONTDs and in CNTDs the TDPF was significantly different from controls (p<.001). CONCLUSIONS: The skull base morphology in fetuses with ONTDs differs significantly from cases with CNTDs and normal controls. This is the first study to show that the CSA changes during gestation and that it is a reliable imaging biomarker to distinguish between ONTDs and CNTDs, independent of the morphology of the spinal defect

Fetal eye movements on magnetic resonance imaging.

OBJECTIVES: Eye movements are the physical expression of upper fetal brainstem function. Our aim was to identify and differentiate specific types of fetal eye movement patterns using dynamic MRI sequences. Their occurrence as well as the presence of conjugated eyeball motion and consistently parallel eyeball position was systematically analyzed. METHODS: Dynamic SSFP sequences were acquired in 72 singleton fetuses (17-40 GW, three age groups [17-23 GW, 24-32 GW, 33-40 GW]). Fetal eye movements were evaluated according to a modified classification originally published by Birnholz (1981): Type 0: no eye movements; Type I: single transient deviations; Type Ia: fast deviation, slower reposition; Type Ib: fast deviation, fast reposition; Type II: single prolonged eye movements; Type III: complex sequences; and Type IV: nystagmoid. RESULTS: In 95.8% of fetuses, the evaluation of eye movements was possible using MRI, with a mean acquisition time of 70 seconds. Due to head motion, 4.2% of the fetuses and 20.1% of all dynamic SSFP sequences were excluded. Eye movements were observed in 45 fetuses (65.2%). Significant differences between the age groups were found for Type I (p = 0.03), Type Ia (p = 0.031), and Type IV eye movements (p = 0.033). Consistently parallel bulbs were found in 27.3-45%. CONCLUSIONS: In human fetuses, different eye movement patterns can be identified and described by MRI in utero. In addition to the originally classified eye movement patterns, a novel subtype has been observed, which apparently characterizes an important step in fetal brainstem development. We evaluated, for the first time, eyeball position in fetuses. Ultimately, the assessment of fetal eye movements by MRI yields the potential to identify early signs of brainstem dysfunction, as encountered in brain malformations such as Chiari II or molar tooth malformations

Impact of selected baking and vacuum cooling parameters on the quality of toast bread

Erworben im Rahmen der Schweizer Nationallizenzen (http://www.nationallizenzen.ch)​Vacuum cooling of baked goods can deliver many advantages in terms of product quality and productivity, such as higher volumes and shorter cooling times. However, the associated high costs and the need to adjust baking protocols are of relevance and more information is needed. This paper examines the influence of two main baking protocol parameters on the quality of toast bread, i.e. oven temperature and baking time reduction. Resulting toast bread characteristics including specific bread volume, concavity, browning index, crust and crumb hardness and aw-value were analysed as well as process-dependent core temperature and water loss. In order to compensate for water loss during vacuum cooling and still achieve optimal toast bread quality, a final bread core temperature of 98 °C at the end of baking gave best results, regardless of oven temperature. It was further shown that cooling time can be reduced by a factor of 10 if the baking protocol is optimally adjusted, hinting at a huge potential to increase productivity for industrial applications. In summary, it can be stated that vacuum cooling requires a tailored reduction in baking time in order to compensate for water loss from vacuum cooling while retaining sufficient structural cohesion to resist deformation of the bread

Methodische Optimierung von Modellansätzen zur Schadstoffbilanzierung in Flussgebietseinheiten zur Förderung der Umsetzungsstrategie zur Wasserrahmenrichtlinie. Endbericht für das Umweltbundesamt-Vorhaben FZK: 370 822 202/01

Im Rahmen einer Machbarkeitsstudie wurden bestehende Quantifizierungsansätze des Modellsystems MONERIS methodisch weiterentwickelt und hinsichtlich ihrer Eignung für die Modellierung auf der Skala großer Flussgebiete getestet. Zudem wurden räumlich und zeitlich höher aufgelöste Eingangsdatensätze implementiert. Auf Grund ihrer Bedeutung für Schadstoffeinträge wurden die Ansätze und Methoden für die Wasserbilanz, Kanalisationssysteme, Erosion und Sedimenteintragsverhältnis, gewässerinterne Retention von partikulär transportierten Schadstoffen und messtechnische Erfassung von Gewässerfrachten im Hochwasserfall weiterentwickelt. Zudem wurden die Eingangsdaten für die Eintragspfade Kanalisationssysteme und die Erosion für die deutschen Einzugsgebiete räumlich und zeitlich höher aufgelöst. Darüber hinaus wurde ein konsistentes und transparentes Instrumentarium zur Quantifizierung und Visualisierung der Stoffeinträge in die Oberflächengewässer entwickelt, mit dessen Hilfe die Berichtspflichten erfüllt werden können. Die Architektur von MoRE erlaubt dem Nutzer, ohne Programmierkenntnisse die Basisvariante durch andere Eingangsdaten und Quantifizierungsansätze zu ergänzen sowie weitere Stoffgruppen einzubinden. Somit entspricht das Werkzeug allen Anforderungen an die Fortschreibung und Weiterentwicklungsfähigkeit im Hinblick auf Szenario-Berechnungen

Methodical Optimization of Model Approaches on Pollutant Balancing in River Basin Districts to Promote the Implementation Strategy for the Water Framework Directive. Final Report on the Project FZK: 370 822 202/01

Within a feasibility study the existing quantification approaches of the model system MONERIS have been methodically developed and their adequacy for modeling in the scale of large river basins has been tested. Additionally, input data sets of spatially and temporally higher resolution have been implemented. The following approaches and methods have been developed based on their relevance for pollutant emissions: water balance and runoff components, sewer systems, erosion and sediment delivery into surface waters, in-stream retention of particulately transported pollutants and the metrological recording of river loads in case of floods. Furthermore, a consistent and transparent instrument for quantifying and visualizing emissions into surface waters has been developed which will facilitate the reporting commitments. The architecture of MoRE allows users without any knowledge of programing to be able to add other input data and quantification approaches as well as embed other substance groups. Thus this instrument complies with the follow-up and development capabilities concerning the consideration of scenarios