The ecdysteroidome of Drosophila: influence of diet and development

Ecdysteroids are the hormones regulating development, physiology and fertility in arthropods, which synthesize them exclusively from dietary sterols. But how dietary sterol diversity influences the ecdysteroid profile, how animals ensure the production of desired hormones and whether there are functional differences between different ecdysteroids produced in vivo remains unknown. This is because currently there is no analytical technology for unbiased, comprehensive and quantitative assessment of the full complement of endogenous ecdysteroids. We developed a new LC-MS/MS method to screen the entire chemical space of ecdysteroid-related structures and to quantify known and newly discovered hormones and their catabolites. We quantified the ecdysteroidome in Drosophila melanogaster and investigated how the ecdysteroid profile varies with diet and development. We show that Drosophila can produce four different classes of ecdysteroids, which are obligatorily derived from four types of dietary sterol precursors. Drosophila makes makisterone A from plant sterols and epi-makisterone A from ergosterol, the major yeast sterol. However, they prefer to selectively utilize scarce ergosterol precursors to make a novel hormone 24,28-dehydromakisterone A and trace cholesterol to synthesize 20-hydroxyecdysone. Interestingly, epi-makisterone A supports only larval development, whereas all other ecdysteroids allow full adult development. We suggest that evolutionary pressure against producing epi-C-24 ecdysteroids might explain selective utilization of ergosterol precursors and the puzzling preference for cholesterol.Max Planck Geselleschaft, Deutsche Forschungsgemeinschaft (TRR 83, projects A17 and A19), European Molecular Biology Organization Long Term Fellowship, University Pierre and Marie Curie

Enhancing the utility of antroduodenal manometry in pediatric intestinal pseudo-obstruction

BACKGROUND: Antroduodenal manometry (ADM) and histopathology are currently employed to aid the diagnosis of pediatric intestinal pseudo-obstruction (PIPO). Limited data are available on the reliability of ADM analysis and its correlation with histopathology. We aimed to develop a protocol for enhanced analysis of ADM contractile patterns, including a scoring system, and explore whether this provided better correlation with histopathology. METHODS: Children referred with suspected PIPO between April 2012-December 2019 who underwent both ADM and full-thickness biopsies were included. ADM tracings were analyzed using both standard (conventional ADM) and novel (enhanced ADM) motility parameters. A novel ADM score (GLASS score) was generated based on the enhanced ADM analysis. Conventional and enhanced ADM analyses were then correlated with histopathology. RESULTS: Forty patients were included. Using conventional clinical criteria, 29 of these were diagnosed with PIPO and the other 11 with non-PIPO diagnoses. Twenty-three of the PIPO patients had abnormal histopathology: 6 myopathy, 4 neuropathy, 3 neuro-myopathy, and 10 non-specific changes. No agreement in diagnosis was found between conventional ADM analysis and histopathology (ϰ = 0.068; p = 0.197), whereas the latter significantly correlated with enhanced ADM analysis (ϰ = 0.191; p = 0.003). The enhanced ADM score was significantly higher in PIPO versus non-PIPO (16.0 vs. 8.0; p < 0.001). CONCLUSIONS: As opposed to conventional analysis protocols, the newly developed enhanced ADM analysis and associated score is not only able to discriminate between PIPO and non-PIPO patients, but also between distinct histopathological pathologies. Further studies are required to assess the utility of enhanced ADM analysis in larger populations

On two problems in graph Ramsey theory

We study two classical problems in graph Ramsey theory, that of determining the Ramsey number of bounded-degree graphs and that of estimating the induced Ramsey number for a graph with a given number of vertices. The Ramsey number r(H) of a graph H is the least positive integer N such that every two-coloring of the edges of the complete graph $K_N$ contains a monochromatic copy of H. A famous result of Chv\'atal, R\"{o}dl, Szemer\'edi and Trotter states that there exists a constant c(\Delta) such that r(H) \leq c(\Delta) n for every graph H with n vertices and maximum degree \Delta. The important open question is to determine the constant c(\Delta). The best results, both due to Graham, R\"{o}dl and Ruci\'nski, state that there are constants c and c' such that 2^{c' \Delta} \leq c(\Delta) \leq 2^{c \Delta \log^2 \Delta}. We improve this upper bound, showing that there is a constant c for which c(\Delta) \leq 2^{c \Delta \log \Delta}. The induced Ramsey number r_{ind}(H) of a graph H is the least positive integer N for which there exists a graph G on N vertices such that every two-coloring of the edges of G contains an induced monochromatic copy of H. Erd\H{o}s conjectured the existence of a constant c such that, for any graph H on n vertices, r_{ind}(H) \leq 2^{c n}. We move a step closer to proving this conjecture, showing that r_{ind} (H) \leq 2^{c n \log n}. This improves upon an earlier result of Kohayakawa, Pr\"{o}mel and R\"{o}dl by a factor of \log n in the exponent.Comment: 18 page

Chromosphere of K giant stars Geometrical extent and spatial structure detection

We aim to constrain the geometrical extent of the chromosphere of non-binary K giant stars and detect any spatial structures in the chromosphere. We performed observations with the CHARA interferometer and the VEGA beam combiner at optical wavelengths. We observed seven non-binary K giant stars. We measured the ratio of the radii of the photosphere to the chromosphere using the interferometric measurements in the Halpha and the Ca II infrared triplet line cores. For beta Ceti, spectro-interferometric observations are compared to an non-local thermal equilibrium (NLTE) semi-empirical model atmosphere including a chromosphere. The NLTE computations provide line intensities and contribution functions that indicate the relative locations where the line cores are formed and can constrain the size of the limb-darkened disk of the stars with chromospheres. We measured the angular diameter of seven K giant stars and deduced their fundamental parameters: effective temperatures, radii, luminosities, and masses. We determined the geometrical extent of the chromosphere for four giant stars. The chromosphere extents obtained range between 16% to 47% of the stellar radius. The NLTE computations confirm that the Ca II/849 nm line core is deeper in the chromosphere of ? Cet than either of the Ca II/854 nm and Ca II/866 nm line cores. We present a modified version of a semi-empirical model atmosphere derived by fitting the Ca II triplet line cores of this star. In four of our targets, we also detect the signature of a differential signal showing the presence of asymmetries in the chromospheres. Conclusions. It is the first time that geometrical extents and structure in the chromospheres of non-binary K giant stars are determined by interferometry. These observations provide strong constrains on stellar atmosphere models.Comment: 10 pages, 12 figure

Disulfide-activated protein kinase G Iα regulates cardiac diastolic relaxation and fine-tunes the Frank-Starling response.

The Frank-Starling mechanism allows the amount of blood entering the heart from the veins to be precisely matched with the amount pumped out to the arterial circulation. As the heart fills with blood during diastole, the myocardium is stretched and oxidants are produced. Here we show that protein kinase G Iα (PKGIα) is oxidant-activated during stretch and this form of the kinase selectively phosphorylates cardiac phospholamban Ser16-a site important for diastolic relaxation. We find that hearts of Cys42Ser PKGIα knock-in (KI) mice, which are resistant to PKGIα oxidation, have diastolic dysfunction and a diminished ability to couple ventricular filling with cardiac output on a beat-to-beat basis. Intracellular calcium dynamics of ventricular myocytes isolated from KI hearts are altered in a manner consistent with impaired relaxation and contractile function. We conclude that oxidation of PKGIα during myocardial stretch is crucial for diastolic relaxation and fine-tunes the Frank-Starling response

Region of Excessive Flux of PeV Cosmic Rays in the Direction Toward Pulsars PSR J1840+5640 and LAT PSR J1836+5925

An analysis of arrival directions of extensive air showers (EAS) registered with the EAS MSU and EAS-1000 prototype arrays has revealed a region of excessive flux of PeV cosmic rays in the direction toward pulsars PSR J1840+5640 and LAT PSR J1836+5925 at significance level up to 4.5sigma. The first of the pulsars was discovered almost 30 years ago and is a well-studied old radio pulsar located at the distance of 1.7pc from the Solar system. The second pulsar belongs to a new type of pulsars, discovered by the space gamma-ray observatory Fermi, pulsations of which are not observed in optical and radio wavelengths but only in the gamma-ray range of energies (gamma-ray-only pulsars). In our opinion, the existence of the region of excessive flux of cosmic rays registered with two different arrays provides a strong evidence that isolated pulsars can give a noticeable contribution to the flux of Galactic cosmic rays in the PeV energy range.Comment: 14 pages; v.2: a few remarks to match a version accepted for Astronomy Letters added. They can be found by redefining the \NEW command in the preamble of the LaTeX fil

A survey of transcutaneous blood gas monitoring among European neonatal intensive care units

BACKGROUND: PCO(2 )and PO(2 )are important monitoring parameters in neonatal intensive care units (NICU). Compared to conventional blood gas measurements that cause significant blood loss in preterms, transcutaneous (tc) measurements allow continuous, non-invasive monitoring of blood gas levels. The aim of the study was to survey the usage and opinions among German speaking NICUs concerning tc blood gas monitoring. METHODS: A questionnaire was developed and sent to 56 head nurses of different NICUs in Germany, Switzerland and Austria. RESULTS: A completely answered questionnaire was obtained from 41 NICUs. In two of these units tc measurements are not performed. In most NICUs (77%), both P(tc)O(2 )and P(tc)CO(2 )are measured simultaneously. Most units change the sensors every 3 hours; however, the recommended temperature of 44°C is used in only 15% of units. In only 8% of units are arterial blood gases obtained to validate tc values. Large variations were found concerning the targeted level of oxygen saturation [median upper limit: 95% (range 80–100%); median lower limit: 86% (range 75–93%)] and PO(2 )[median upper limit: 70 mmHg (range 45–90 mmHg); median lower limit: 44 mmHg (range 30–60 mmHg)]. CONCLUSION: Our survey shows that the use of tc monitors remains widespread among German speaking NICUs, despite earlier data suggesting that their use had been abandoned in many NICUs worldwide. In addition, we suggest that the current method of monitoring oxygenation may not prevent hyperoxemia in preterm infants

Automatic Network Fingerprinting through Single-Node Motifs

Complex networks have been characterised by their specific connectivity patterns (network motifs), but their building blocks can also be identified and described by node-motifs---a combination of local network features. One technique to identify single node-motifs has been presented by Costa et al. (L. D. F. Costa, F. A. Rodrigues, C. C. Hilgetag, and M. Kaiser, Europhys. Lett., 87, 1, 2009). Here, we first suggest improvements to the method including how its parameters can be determined automatically. Such automatic routines make high-throughput studies of many networks feasible. Second, the new routines are validated in different network-series. Third, we provide an example of how the method can be used to analyse network time-series. In conclusion, we provide a robust method for systematically discovering and classifying characteristic nodes of a network. In contrast to classical motif analysis, our approach can identify individual components (here: nodes) that are specific to a network. Such special nodes, as hubs before, might be found to play critical roles in real-world networks.Comment: 16 pages (4 figures) plus supporting information 8 pages (5 figures