A novel IEF peptide fractionation method reveals a detailed profile of N-terminal Acetylation in chemotherapy-responsive and -resistant ovarian cancer cells

Although acetylation is regarded as a common protein modification, a detailed proteome wide profile of this posttranslational modification may reveal important biological insight regarding differential acetylation of individual proteins. Here we optimised a novel peptide IEF fractionation method for use prior to LC-MS/MS analysis in order to obtain a more in depth coverage of N-terminally acetylated proteins from complex samples. Application of the method to the analysis of the serous ovarian cancer cell line OVCAR-5 identified 341 N-terminally acetylated proteins, 23 of which are previously un-reported. The protein peptidyl-prolyl cis-trans isomerase A (PPIA) was detected in both the N-terminally acetylated and un-modified forms, and was further analysed by data independent acquisition in Carboplatin responsive parental OVCAR-5 cells and Carboplatin resistant OVCAR-5 cells. This revealed a higher ratio of un-acetylated to acetylated N-terminal PPIA in the parental compared to the Carboplatin resistant OVCAR-5 cells, and a 4.1-fold increase in PPIA abundance overall in the parental cells relative to Carboplatin-resistant OVCAR-5 cells (P = 0.015). In summary, the novel IEF peptide fractionation method presented here is robust, reproducible, and can be applied to the profiling of N-terminally acetylated proteins. All mass spectrometry data is available as a ProteomeXchange repository (PXD003547).Florian Weiland, Georgia Arentz, Manuela Klingler-Hoffmann, Peter McCarthy, Noor A. Lokman, Gurjeet Kaur, Martin K. Oehler, and Peter Hoffman

Reverberation chambers a la carte: An overview of the different mode-stirring techniques

Reverberation chambers (RC), a name inspired in room acoustics, are also known in literature as reverberating, reverb, mode-stirred or mode-tuned chambers. In their basic form, they consist of a shielded metallic enclosure, forming a cavity resonator, together with some mode-stirring mechanism. The main goal of such stirring mechanism is to generate an amplitude-varying electromagnetic field that is ideally statistically uniform

Gallot-Tanno Theorem for closed incomplete pseudo-Riemannian manifolds and applications

We extend the Gallot-Tanno Theorem to closed pseudo-Riemannian manifolds. It is done by showing that if the cone over a manifold admits a parallel symmetric $(0,2)-$tensor then it is Riemannian. Applications of this result to the existence of metrics with distinct Levi-Civita connections but having the same unparametrized geodesics and to the projective Obata conjecture are given. We also apply our result to show that the holonomy group of a closed $(O(p+1,q),S^{p,q})$-manifold does not preserve any nondegenerate splitting of $\R^{p+1,q}$.Comment: minor correction

Land-use impacts of Brazilian wind power expansion

While wind power is a low-carbon renewable energy technology with relatively little land footprint, the necessary infrastructure expansion still has land-related environmental impacts. Brazil has seen more than a ten-fold increase in wind power capacity in the last decade. However, little is known about these impacts of wind power generation in Brazil compared to other world regions, although Brazilian wind power infrastructure is concentrated in the least protected ecosystems that are prone to degradation, desertification and species extinction. This study focuses on land-use impacts of past wind power generation development in four Brazilian federal states, covering 80% of the country's installed capacity. We assessed their spatial installation patterns, associated land-use and land cover change in the period before installation until 2018, and potential alternative installation locations, using a detailed wind turbine location database in combination with a high-resolution land-use and land cover map. In contrast to wind parks built in Europe, we found that 62% of the studied wind park area was covered by native vegetation and coastal sands. Overall, 3.2% of the total wind cluster area was converted from native vegetation to anthropogenic use. Wind parks installed mainly on native vegetation, on average, underwent higher land-use change compared to other wind parks. As Brazil intends to more than double its current wind power capacities by 2029, we explored possibilities to reduce environmental risks due to wind power expansion. We showed that this is feasible by integrating wind parks into human-altered areas, as sufficient wind resources there are available

Effective Viscosity of a Dilute Suspension of Membrane-bound Inclusions

When particulate suspensions are sheared, perturbations in the shear flows around the rigid particles increase the local energy dissipation, so that the viscosity of the suspension is effectively higher than that of the solvent. For bulk (three-dimensional) fluids, understanding this viscosity enhancement is a classic problem in hydrodynamics that originated over a century ago with Einstein's study of a dilute suspension of spherical particles. \cite{Einstein1} In this paper, we investigate the analogous problem of the effective viscosity of a suspension of disks embedded in a two-dimensional membrane or interface. Unlike the hydrodynamics of bulk fluids, low-Reynolds number membrane hydrodynamics is characterized by an inherent length scale generated by the coupling of the membrane to the bulk fluids that surround it. As a result, we find that the size of the particles in the suspension relative to this hydrodynamic length scale has a dramatic effect on the effective viscosity of the suspension. Our study also helps to elucidate the mathematical tools needed to solve the mixed boundary value problems that generically arise when considering the motion of rigid inclusions in fluid membranes.Comment: 33 pages, 4 figures (preprint); submitted to Physics of Fluid

Notes on a paper of Mess

These notes are a companion to the article "Lorentz spacetimes of constant curvature" by Geoffrey Mess, which was first written in 1990 but never published. Mess' paper will appear together with these notes in a forthcoming issue of Geometriae Dedicata.Comment: 26 page

Pulsar-wind nebulae and magnetar outflows: observations at radio, X-ray, and gamma-ray wavelengths

We review observations of several classes of neutron-star-powered outflows: pulsar-wind nebulae (PWNe) inside shell supernova remnants (SNRs), PWNe interacting directly with interstellar medium (ISM), and magnetar-powered outflows. We describe radio, X-ray, and gamma-ray observations of PWNe, focusing first on integrated spectral-energy distributions (SEDs) and global spectral properties. High-resolution X-ray imaging of PWNe shows a bewildering array of morphologies, with jets, trails, and other structures. Several of the 23 so far identified magnetars show evidence for continuous or sporadic emission of material, sometimes associated with giant flares, and a few possible "magnetar-wind nebulae" have been recently identified.Comment: 61 pages, 44 figures (reduced in quality for size reasons). Published in Space Science Reviews, "Jets and Winds in Pulsar Wind Nebulae, Gamma-ray Bursts and Blazars: Physics of Extreme Energy Release

Tc-knirps plays different roles in the specification of antennal and mandibular parasegment boundaries and is regulated by a pair-rule gene in the beetle Tribolium castaneum

Background: The Drosophila larval head is evolutionarily derived at the genetic and morphological level. In the beetle Tribolium castaneum, development of the larval head more closely resembles the ancestral arthropod condition. Unlike in Drosophila, a knirps homologue (Tc-kni) is required for development of the antennae and mandibles. However, published Tc-kni data are restricted to cuticle phenotypes and Tc-even-skipped and Tc-wingless stainings in knockdown embryos. Hence, it has remained unclear whether the entire antennal and mandibular segments depend on Tc-kni function, and whether the intervening intercalary segment is formed completely. We address these questions with a detailed examination of Tc-kni function. Results: By examining the expression of marker genes in RNAi embryos, we show that Tc-kni is required only for the formation of the posterior parts of the antennal and mandibular segments (i.e. the parasegmental boundaries). Moreover, we find that the role of Tc-kni is distinct in these segments: Tc-kni is required for the initiation of the antennal parasegment boundary, but only for the maintenance of the mandibular parasegmental boundary. Surprisingly, Tc-kni controls the timing of expression of the Hox gene Tc-labial in the intercalary segment, although this segment does form in the absence of Tc-kni function. Unexpectedly, we find that the pair-rule gene Tc-even-skipped helps set the posterior boundary of Tc-kni expression in the mandible. Using the mutant antennaless, a likely regulatory Null mutation at the Tc-kni locus, we provide evidence that our RNAi studies represent a Null situation. Conclusions: Tc-kni is required for the initiation of the antennal and the maintenance of the mandibular parasegmental boundaries. Tc-kni is not required for specification of the anterior regions of these segments, nor the intervening intercalary segment, confirming that Tc-kni is not a canonical 'gap-gene'. Our finding that a gap gene orthologue is regulated by a pair rule gene adds to the view that the segmentation gene hierarchies differ between Tribolium and Drosophila upstream of the pair rule gene level. In Tribolium, as in Drosophila, head and trunk segmentation gene networks cooperate to pattern the mandibular segment, albeit involving Tc-kni as novel component

European Malignant Hyperthermia Group guidelines for investigation of malignant hyperthermia susceptibility

It is 30 yr since the British Journal of Anaesthesia published the first consensus protocol for the laboratory diagnosis of malignant hyperthermia susceptibility from the European Malignant Hyperthermia Group. This has subsequently been used in more than 10 000 individuals worldwide to inform use of anaesthetic drugs in these patients with increased risk of developing malignant hyperthermia during general anaesthesia, representing an early and successful example of stratified medicine. In 2001, our group also published a guideline for the use of DNA-based screening of malignant hyperthermia susceptibility. We now present an updated and complete guideline for the diagnostic pathway for patients potentially at increased risk of developing malignant hyperthermia. We introduce the new guideline with a narrative commentary that describes its development, the changes to previously published protocols and guidelines, and new sections, including recommendations for patient referral criteria and clinical interpretation of laboratory finding