Modulation of sterol homeostasis by the Cdc42p effectors Cla4p and Ste20p in the yeast Saccharomyces cerevisiae

This article is available open access through the publisher’s website at the link below. Copyright @ 2009 The Authors.The conserved Rho-type GTPase Cdc42p is a key regulator of signal transduction and polarity in eukaryotic cells. In the yeast Saccharomyces cerevisiae, Cdc42p promotes polarized growth through the p21-activated kinases Ste20p and Cla4p. Previously, we demonstrated that Ste20p forms a complex with Erg4p, Cbr1p and Ncp1p, which all catalyze important steps in sterol biosynthesis. CLA4 interacts genetically with ERG4 and NCP1. Furthermore, Erg4p, Ncp1p and Cbr1p play important roles in cell polarization during vegetative growth, mating and filamentation. As Ste20p and Cla4p are involved in these processes it seems likely that sterol biosynthetic enzymes and p21-activated kinases act in related pathways. Here, we demonstrate that the deletion of either STE20 or CLA4 results in increased levels of sterols. In addition, higher concentrations of steryl esters, the storage form of sterols, were observed in cla4Δ cells. CLA4 expression from a multicopy plasmid reduces enzyme activity of Are2p, the major steryl ester synthase, under aerobic conditions. Altogether, our data suggest that Ste20p and Cla4p may function as negative modulators of sterol biosynthesis. Moreover, Cla4p has a negative effect on steryl ester formation. As sterol homeostasis is crucial for cell polarization, Ste20p and Cla4p may regulate cell polarity in part through the modulation of sterol homeostasis.Deutsche Forschungsgemeinschaft and the Austrian FWF

Effect of Human Exogenous Leukocyte Interferon in Cytomegalovirus Infections

Human leukocyte interferon was injected into nine patients with cytomegalovirus infections; four of these patients were congenitally infected, and five had acquired infections. In three patients viruria was completely inhibited. In five patients viral excretion in the urine was only transiently inhibited. Viremia was not significantly suppressed. The lymphocyte response to phytohemagglutinin was suppressed in two patient

A compact unc45b-promoter drives muscle-specific expression in zebrafish and mouse

Summary: Gene therapeutic approaches to cure genetic diseases require tools to express the rescuing gene exclusively within the affected tissues. Viruses are often chosen as gene transfer vehicles but they have limited capacity for genetic information to be carried and transduced. In addition, to avoid off-target effects the therapeutic gene should be driven by a tissue-specific promoter in order to ensure expression in the target organs, tissues, or cell populations. The larger the promoter, the less space will be left for the respective gene. Thus, there is a need for small but tissue-specific promoters. Here, we describe a compact unc45b promoter fragment of 195 bp that retains the ability to drive gene expression exclusively in skeletal and cardiac muscle in zebrafish and mouse. Remarkably, the described unc45b promoter fragment not only drives muscle-specific expression but presents heat-shock inducibility, allowing a temporal and spatial quantity control of (trans)gene expression. Here, we demonstrate that the transgenic expression of the smyd1b gene driven by the unc45b promoter fragment is able to rescue the embryonically lethal heart and skeletal muscle defects in smyd1b-deficient flatline mutant zebrafish. Our findings demonstrate that the described muscle-specific unc45b promoter fragment might be a valuable tool for the development of genetic therapies in patients suffering from myopathies. genesis 54:431–438, 2016. © 2016 The Authors. Genesis Published by Wiley Periodicals, Inc

The asymmetric drift, the local standard of rest, and implications from RAVE data

Context. The determination of the local standard of rest (LSR), which corresponds to the measurement of the peculiar motion of the Sun based on the derivation of the asymmetric drift of stellar populations, is still a matter of debate. The classical value of the tangential peculiar motion of the Sun with respect to the LSR was challenged in recent years, claiming a significantly larger value. Aims. We present an improved Jeans analysis, which allows a better interpretation of the measured kinematics of stellar populations in the Milky Way disc. We show that the Radial Velocity Experiment (RAVE) sample of dwarf stars is an excellent data set to derive tighter boundary conditions to chemodynamical evolution models of the extended solar neighbourhood. Methods. We propose an improved version of the Stromberg relation with the radial scalelengths as the only unknown. We redetermine the asymmetric drift and the LSR for dwarf stars based on RAVE data. Additionally, we discuss the impact of adopting a different LSR value on the individual scalelengths of the subpopulations. Results. Binning RAVE stars in metallicity reveals a bigger asymmetric drift (corresponding to a smaller radial scalelength) for more metal-rich populations. With the standard assumption of velocity-dispersion independent radial scalelengths in each metallicity bin, we redetermine the LSR. The new Stromberg equation yields a joint LSR value of V-circle dot = 3.06 +/- 0.68 km s(-1), which is even smaller than the classical value based on Hipparcos data. The corresponding radial scalelength increases from 1.6 kpc for the metal-rich bin to 2.9 kpc for the metal-poor bin, with a trend of an even larger scalelength for young metal-poor stars. When adopting the recent Schonrich value of V-circle dot = 12.24 km s(-1) for the LSR, the new Stromberg equation yields much larger individual radial scalelengths of the RAVE subpopulations, which seem unphysical in part. Conclusions. The new Stromberg equation allows a cleaner interpretation of the kinematic data of disc stars in terms of radial scalelengths. Lifting the LSR value by a few km s(-1) compared to the classical value results in strongly increased radial scalelengths with a trend of smaller values for larger velocity dispersions

Chemical gradients in the Milky Way from the RAVE data. II. Giant stars

We provide new constraints on the chemo-dynamical models of the Milky Way by measuring the radial and vertical chemical gradients for the elements Mg, Al, Si, Ti, and Fe in the Galactic disc and the gradient variations as a function of the distance from the Galactic plane ($Z$). We selected a sample of giant stars from the RAVE database using the gravity criterium 1.7$<$log g$<$2.8. We created a RAVE mock sample with the Galaxia code based on the Besan\c con model and selected a corresponding mock sample to compare the model with the observed data. We measured the radial gradients and the vertical gradients as a function of the distance from the Galactic plane $Z$ to study their variation across the Galactic disc. The RAVE sample exhibits a negative radial gradient of $d[Fe/H]/dR=-0.054$ dex kpc$^{-1}$ close to the Galactic plane ($|Z|<0.4$ kpc) that becomes flatter for larger $|Z|$. Other elements follow the same trend although with some variations from element to element. The mock sample has radial gradients in fair agreement with the observed data. The variation of the gradients with $Z$ shows that the Fe radial gradient of the RAVE sample has little change in the range $|Z|\lesssim0.6$ kpc and then flattens. The iron vertical gradient of the RAVE sample is slightly negative close to the Galactic plane and steepens with $|Z|$. The mock sample exhibits an iron vertical gradient that is always steeper than the RAVE sample. The mock sample also shows an excess of metal-poor stars in the [Fe/H] distributions with respect to the observed data. These discrepancies can be reduced by decreasing the number of thick disc stars and increasing their average metallicity in the Besan\c con model.Comment: 13 pages, 9 figures, 5 tables, A&A accepte

Can Neutron Star Mergers Alone Explain the r-process Enrichment of the Milky Way?

© 2023. The Author(s). Published by the American Astronomical Society. This is an open access article under the terms of the Creative Commons Attribution License, https://creativecommons.org/licenses/by/4.0/Comparing Galactic chemical evolution models to the observed elemental abundances in the Milky Way, we show that neutron star mergers can be a leading r-process site only if at low metallicities such mergers have very short delay times and significant ejecta masses that are facilitated by the masses of the compact objects. Namely, black hole–neutron star mergers, depending on the black hole spins, can play an important role in the early chemical enrichment of the Milky Way. We also show that none of the binary population synthesis models used in this Letter, i.e., COMPAS, StarTrack, Brussels, ComBinE, and BPASS, can currently reproduce the elemental abundance observations. The predictions are problematic not only for neutron star mergers, but also for Type Ia supernovae, which may point to shortcomings in binary evolution models.Peer reviewe

Palliative care for the elderly - developing a curriculum for nursing and medical students

<p>Abstract</p> <p>Background</p> <p>Delivering palliative care to elderly, dying patients is a present and future challenge. In Germany, this has been underlined by a 2009 legislation implementing palliative care as compulsory in the medical curriculum. While the number of elderly patients is increasing in many western countries multimorbidity, dementia and frailty complicate care. Teaching palliative care of the elderly to an interprofessional group of medical and nursing students can help to provide better care as acknowledged by the ministry of health and its expert panels.</p> <p>In this study we researched and created an interdisciplinary curriculum focussing on the palliative care needs of the elderly which will be presented in this paper.</p> <p>Methods</p> <p>In order to identify relevant learning goals and objectives for the curriculum, we proceeded in four subsequent stages.</p> <p>We searched international literature for existing undergraduate palliative care curricula focussing on the palliative care situation of elderly patients; we searched international literature for palliative care needs of the elderly. The searches were sensitive and limited in nature. Mesh terms were used where applicable. We then presented the results to a group of geriatrics and palliative care experts for critical appraisal. Finally, the findings were transformed into a curriculum, focussing on learning goals, using the literature found.</p> <p>Results</p> <p>The literature searches and expert feedback produced a primary body of results. The following deduction domains emerged: Geriatrics, Palliative Care, Communication & Patient Autonomy and Organisation & Social Networks. Based on these domains we developed our curriculum.</p> <p>Conclusions</p> <p>The curriculum was successfully implemented following the Kern approach for medical curricula. The process is documented in this paper. The information given may support curriculum developers in their search for learning goals and objectives.</p